Reduced fecundity of fat women

J Womens Health (Larchmt). 2009 May;18(5):633-6.

The relationship between obesity and fecundity.

Yilmaz N, Kilic S, Kanat-Pektas M, Gulerman C, Mollamahmutoglu L.

OBJECTIVE: Obesity is an important factor that might reduce fecundity. In order to determine the underlying physiological mechanisms and risk factors, the obesity-fecundity association is investigated in relation to parity, menstrual cycle regularity, smoking habits, and age. METHODS: This was a retrospective cohort study of 22,840 women who gave birth between January 2006 and January 2007 in the Dr Zekai Tahir Burak Women's Health Research and Education Hospital. Age, parity, prepregnancy body mass index (BMI) values, time to pregnancy data related to smoking, and reproductive, medical, and gynecological history were obtained from the medical records. RESULTS: Fecundity was reduced for overweight and obese women compared with optimal weight women, and this reduction was more evident for obese primiparous women. Fecundity remained reduced for overweight and obese women with normal menstrual cycles. Obese and overweight women were found to smoke significantly more than the optimal weight group. CONCLUSIONS: Obesity was found to be associated with reduced fecundity for all weight-adjusted groups of women and persisted for women with regular cycles. Weight loss should be encouraged initially during the treatment of infertile overweight and obese women.

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European admixture and obesity traits in African Americans

Obesity (Silver Spring). doi:10.1038/oby.2009.282

Admixture Mapping of Obesity-related Traits in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study.

Cheng CY, Reich D, Coresh J, Boerwinkle E, Patterson N, Li M, North KE, Tandon A, Bailey-Wilson JE, Wilson JG, Kao WH.

Obesity is an important cause of morbidity and mortality worldwide. In the United States, the prevalence of obesity is higher in African Americans than whites, even after adjustment for socioeconomic status (SES). This leads to the hypothesis that differences in genetic background may contribute to racial/ethnic differences in obesity-related traits. We tested this hypothesis by conducting a genome-wide admixture mapping scan using 1,350 ancestry-informative single-nucleotide polymorphisms (SNPs) in 3,531 self-identified blacks from the Atherosclerosis Risk in Communities (ARIC) study. We used these markers to estimate the overall proportions of European ancestry (PEAs) for each individual and then scanned for the association between PEA and obesity-related traits (both continuous and dichotomous) at each locus. The median (interquartile range) PEA was 0.151 (0.115). PEA was inversely correlated with continuous BMI, weight, and subscapular skinfold thickness, even after adjusting for socioeconomic factors. In contrast, PEA was positively correlated with BMI-adjusted waist circumference. Using admixture mapping on dichotomized traits, we identified a locus on 2p23.3 to be suggestively associated with BMI (locus-specific lod = 4.11) and weight (locus-specific lod = 4.07). After adjusting for global PEA, each additional copy of a European ancestral allele at the 2p23.3 peak was associated with a BMI decrease of ~0.92 kg/m(2) (P = 2.9 x 10(-5)). Further mapping in this region on chromosome 2 may be able to uncover causative variants underlying obesity, which may offer insights into the control of energy homeostasis.

Link

European admixture and Body Mass Index in African Americans

While a larger portion of African ancestry in African Americans is associated with higher probability of obesity, a larger portion of African ancestry in a particular locus actually reduced the probability of obesity. This underscores the importance of not relying on first-order approximations (racial identity) when more detailed information is available.

From the paper:

We have carried out admixture mapping analyses to search for genomic regions associated with BMI. This pooled analysis of samples from 14 studies is the largest admixture scan reported to date. In more than 15,000 individuals, we identified a locus on chromosome 5 where greater local European ancestry was associated with higher levels of BMI (P = 5.8×10⁻⁷), and two regions on chromosome X where greater local European ancestry was associated with lower levels of BMI (both P<5.0×10⁻⁶). Each of these three associations was above and beyond the contribution of genome-wide European ancestry, and each reached genome-wide significance.

...

The inverse correlation between BMI and percentage of European ancestry estimated on the genome-wide scale confirmed the results from previous studies of smaller sample size and fewer markers [29],[30]. However, while genome-wide ancestry is likely correlated with local ancestry, it cannot fully capture ancestry information at each locus as there exists variation across the genome in the effects of locus-specific ancestry on obesity. In particular, local European ancestry at 5q13.3 was positively associated with BMI, providing the first evidence of a genome-wide significant ancestry association being in the opposite direction to the overall epidemiological association.

PLoS Genetics doi:10.1371/journal.pgen.1000490

Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X

Ching-Yu Cheng et al.

Abstract

The prevalence of obesity (body mass index (BMI) ≥30 kg/m²) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (ρ = −0.042, P = 1.6×10⁻⁷). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = −3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = −4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI.

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ESHG 2009 abstracts

ESHG 2009 is in two weeks, and there are some very interesting abstracts, including a tantalizing new study on Y-chromosome haplogroup R1b1b2 (R-M269).

Phylogeography of human Y chromosome haplogroup R1b1b2 (R-M269) in Europe

F. Cruciani et al.

The human Y chromosome haplogroup R1b1b2 (R-M269) displays an extremely wide geographic distribution within Europe, with a decreasing frequency cline from Iberia (frequencies up to 90%) towards the Balkans (usually less than 10%). Previous studies have proposed that the observed R1b1b2 frequency cline is due to a population expansion from an Iberian Ice-age refugium after the LGM (Malaspina et al. 1998; Semino et al. 2000).

In this study, we explored the phylogeography of the human Y chromosome haplogroup R1b1b2 by analyzing more than 2,000 males from Europe. The haplogroup-defining marker M269 (Cruciani et al. 2002), and two additional internal markers (U106 and U152, Sims et al 2007) which identify internal branches (R1b1b2g and R1b1b2h) were analyzed. The paragroup R1b1b2*(xR1b1b2g, R1b1b2h) and the haplogroups R1b1b2g and R1b1b2h showed quite different frequency distribution patterns within Europe, with frequency peaks in the Iberian Peninsula, northern Europe and northern Italy/France, respectively. The overall frequency pattern of R1b1b2 haplogroup is suggestive of multiple events of migration and expansion within Europe rather than a single and uniform spread of people from an Iberian Ice-age refugium.

References:

Malaspina et al. (1998) Am J Hum Genet 63:847-860
Semino et al. (2000) Science 290:1155-1159
Cruciani et al. (2002) Am J Hum Genet 70:1197-1214
Sims et al. (2007) Hum Mutat 28:97

Note that in the abstract below, the authors refer to Slavopaionians, not Macedonians.

Y chromosome haplogroup R1a is associated with prostate cancer risk among Macedonian males

D. Plaseska-Karanfilska et al.

Prostate cancer (PC) is one of the most common male-specific cancers. Its incidence varies considerably between populations. Recent surveys suggest that PC is influenced by both genetic and environmental factors, although the etiology of the disease remains unknown in the majority of cases. Certain Y chromosomal lineages have been suggested to predispose individuals to prostate cancer in Japanese population, but no association has been found among Korean and Swedish patients. The aim of this study was to investigate the association between Y chromosomal haplogroups and predisposition to prostate cancer in Macedonian men. We studied 84 PC patients and 126 males from the general population of Macedonian ethnic origin. A total of 28 markers have been studied by multiplex PCR and SNaPshot analysis. Nineteen different Y haplogroups were determined; the most frequent being I1b-P37b, E3b1-M78, R1a-SRY 1532, R1b-P25 and J2b1a-M241. The frequency of R1a was significantly higher in PC patients (20.2%) in comparison with the controls (9.5%) [p=0.027; OR=2.41 (1.09-5.36)]. When stratified according to age, even stronger association was observed between haplogroup R1a and prostate cancer in patients of >65 years of age [p=0.004; OR=3.24 (1.41-7.46)]. Our results suggest that Y chromosome haplogroup R1a is associated with an increased prostate cancer risk in Macedonian men.

The genetic position of Western Brittany (Finistère, France) in the Celtic Y chromosome landscape

K. Rouault et al.

Brittany, a large peninsula located at the western part of France, is of particular interest because of its historical settlement and its relative geographic and cultural isolation. Brittany was invaded by waves of migration from Britain and Ireland between the 4th and 7th centuries and, therefore, belongs to the Brythonic branch of the Insular Celtic language. We have focused our study on the department of Finistère, the most western territorial unit of Brittany, and its administrative and historical areas. To explore the diversity of the Y-chromosome, we analyzed a total of 348 unrelated males using a combination of 23 biallelic markers and 12 microsatellite loci. The molecular analysis revealed that 82.2% of the Y chromosomes fell into haplogroup R1b, placing Finistère within the Western European landscape. Interestingly, at a microgeographical level, differences were detected by the haplogroup R1a* being confined to the south of the department, while haplogroups E3b, F, G, J2, K and R1a1 were found in the north. Nevertheless, geographical distribution of haplogroups and haplotypes suggested territorial homogeneity inside Finistère. Most of the Y-chromosomal gene pool in Finistère is shared with European, especially British, populations, thus corroborating the historical reports of ancient migrations to Brittany. Finally, the results are consistent with those obtained from classic genetic markers and support the Celtic paternal heritage of the Finistère population.

Mitochondrial Genome Diversity in Tungusic-speaking Populations (Even and Evenki) and Resettlement of Arctic Siberia After the Last Glacial Maximum

I. O. Mazunin et al.

The present study includes the Even/Evenki, hunters and reindeer-breeders, sampled from a few localities scattered across their vast geographic range encompassing low Yana-Indigirka-Kolyma in the west and the Sea of Okhotsk coast in the east. The mtDNA data show a very close affinity of the Even/Evenki with the Yukaghir, typical reindeer hunters, dominating in extreme northeastern Siberia until the middle of 18th century but now being on the brink of extinction. We found that the majority of mtDNA diversity in the Tungusic-speaking populations was accounted for by Siberian-East Eurasian lineages C2, C3, D2, D3, D4-D9 and G1. The similarity in the haplogroup C and D mtDNA intrinsic variation between the Even and Yukaghir populations is pronounced and indicates that the Even/Evenki harbor an essential portion of the ancestral Yukaghir pool. The phylogeography of the D4-D9 point to an early Neolithic phase expansion initiated northward to the northern and eastern perimeters of former Beringia. Concerning unique D2* lineage (Volodko et al. 2008), the network analysis encompassing four complete sequences, three of the Yukaghir from the low Indigirka-Kolyma region and one of the Evenk from the upper reaches of the Aldan River would suggest that the founding haplotype (1935-8683-14905) for D2* originated within western part of former Beringia. In the meanwhile, the core of the Even/Evenki mtDNA pool residing in the midst of the Yukaghir ancient territory would represent a recent amalgamation of the remnants of the Yukaghir and northern Tungusic-speakers (Even/Evenki) originated in the mid-Amur region.

X-chromosomal haplotypes in global human populations

V. A. Stepanov, I. Y. Khitrinskaya;

To reconstruct the origin and evolution of X-chromosomal lineages in global human populations we investigated the genetic diversity in 23 population samples (about 1500 individuals totally) using SNP markers in a single linkage disequilibrium region of ZFX gene. About sixty haplotypes belonging to 3 phylogenetic branches (A, B, and F) originated from the single African root were found in the total sample. Branch A includes mostly African haplotypes, whereas four major haplotypes belonging to different sub-branches of B (haplotype E8) and F (haplotypes H4, I3 and I11) were present in Eurasia. Major haplotype of the older branch B (E8) is almost evenly distributed among Eurasian populations. Haplotypes of the younger phylogenetic branches demonstrates clinal distribution with the sharp frequency changes from East to West. Haplotype H4 is presumably “Eastern-Eurasian”. It reaches the highest frequency in Eastern and South-Eastern Asians. Haplotypes I3 and I11 in the contrary show the clear frequency gradient from West to East with the highest frequency in Europeans, moderate frequency in Central Asia, and the minimal frequency in North-East and South-East Asia. The total level of genetic differentiation of global human populations estimated by the analysis of molecular variance of X-chromosomal haplotypes (Fst = 9.1%) is quite high and roughly corresponds to those measured for most other types of genetic markers except Y-chromosomal haplogroups which are characterized by the much higher level of between-population differences.

Dissecting the genetic make-up of Central Eastern Sardinia using a high density set of sex and autosomal markers

L. M. Pardo

Genetic isolates are valuable for identifying genetic variations underlying complex traits. However, prior knowledge of the genetic structure of the isolate is fundamental for carrying-out genome-wide association studies (GWAS) in these populations. The Sardinian population is currently the target of GWAS because of its ancient origin and long-standing isolation. To perform GWAS in Sardinia, we aim to characterize a subpopulation from the archaic area of Central-Eastern Sardinia at the genomic level. We used sex-specific markers (Y-chromosome and mtDNA) to assess the heterogeneity of the founder lineages and the divergence from other populations. In addition, we used a dense set of autosomal markers (SNP 5.0 array, Affymetrix) to investigate genome-wide Linkage Disequilibrium, to construct a Copy Number Variation map and to estimate pair-wise kinship and inbreeding.We first determined Y-chromosome lineages in 256 unrelated Sardinians using biallelic and microsatellite markers. Our analysis showed that the frequency of the major Y haplogroups clearly sets this population apart from other European haplogroups. The analysis of microsatellite markers revealed a high degree of gene diversity. Pairwise kinship and inbreeding were estimated in 113 subjects using 77709 autosomal SNP markers. We found that 16% of the subject pairs shared identical-by descent alleles more often than expected by chance. Furthermore, 60% of the subjects had low inbreeding coefficient values. Our preliminary results confirm that Sardinia is genetically different from other populations, as shown by Y-chromosome markers. The kinship and inbreeding estimates indicate some degree of relatedness among Sardinians, as expected for an isolated population.

Genetic differences between four European populations

V. Moskvina et al.

Population stratification can distort the results of genome-wide association studies (GWAS). One approach to deal with this inflation of the statistic is to estimate the inflation factor and adjust the detection statistic accordingly. However, the evolutionally forces work with different strength in some regions of the human genome, e.g. around the lactase gene (LCT) and the HLA region, making such an adjustment inappropriate.

We examined the population differences in four European populations (Scotland, Ireland, Sweden and Bulgaria) using data from GWAS performed with the Affymetrix 6.0 array at the Broad Institute. We show that there are >20,000 SNPs which are highly (p less than 10-6) significantly stratified between the four populations, after genome wide Bonferroni correction for multiple testing. We then examined the top 20 stratified regions to see what genes might have caused the top differences, using a highly conservative cut-off of p less than 10-40. Some of the loci span genes reported before: hair colour and pigmentation (HERC2, EXOC2), the LCT gene, genes involved in NAD metabolism, and genes involved in immunity (HLA and the Toll-like receptor genes TLR10, TLR 1, TLR 6). Among the top hits were several genes which have not yet been reported as stratified within European populations, indicating that they might also provide a selective advantage. Some involve other immunity genes (CD99, ILT6), but others show no obvious effect on positive selection: several zinc fingers, and most intriguingly, FOXP2, implicated in speech development. Future GWAS should take into consideration any positive associations with these genes.

Genomic runs of homozygosity: population history and disease

R. McQuillan

Runs of homozygosity (ROH), resulting from the inheritance from both parents of identical haplotypes, are abundant in the human genome. ROH length is determined partly by the number of generations since the common ancestor: offspring of cousin matings have long ROH, while the numerous shorter ROH reflect shared ancestry tens and hundreds of generations ago. In studies of European populations we show that Froh, a multipoint estimate of individual autozygosity derived from genomic ROH, distinguishes clearly between subpopulations classified in terms of demographic history and correlates strongly with pedigree-derived inbreeding coefficients. In a global population dataset, analysis of ROH allows categorisation of individuals into four major groups, inferred to have (a) parental relatedness in the last 150 years (many south and west Asians), (b) shared parental ancestry arising hundreds to thousands of years ago through population isolation and restricted effective population size (Ne), but little recent inbreeding (Oceanians, African hunter-gatherers, some European and south Asian isolates), (c) both ancient and recent parental relatedness (Native Americans), and (d) only the background level of shared ancestry relating to continental Ne (east Asians, urban Europeans; African agriculturalists). Long runs of homozygosity are therefore a widespread and underappreciated characteristic of our genomes which record past consanguinity and population isolation and provide a unique record of individual demographic history. Individual ROH measures also allow quantification of the disease risk arising from polygenic recessive effects. We present preliminary data from a survey of the effects of ROH on quantitative disease-related traits and disease risk.

European Lactase Persistence Allele is Associated With Increase in Body Mass Index

J. A. Kettunen et al.

The global prevalence of obesity, usually indexed by body mass index (BMI) cut-offs, has increased significantly in the recent decades, mainly due to positive energy balance. However, the impact of a selection for specific genes cannot be excluded. Here we have tested the association between BMI and one of the best known genetic variants showing strong selective pressure: the functional variant in the cis-regulatory element of the lactase gene. We tested this variant since it is presumed to provide nutritional advantage in specific physical and cultural environments. We found that the variant responsible for lactase persistence among Europeans was also associated with higher BMI in a Nordic population sample (p = 1.3*10-5) of 15 209 individuals, the size of the effect being close to that of FTO. We tested the effect of population stratification and concluded that the association was not due to population substructure.

Body mass index and income in Europe

There seems to be some variation in the strength of the effect, but overall the finding is that women with higher BMI (heavier for their height) tend to make less money than slimmer women.

Economics and Human Biology doi:10.1016/j.ehb.2009.01.006

Income and Body Mass Index in Europe

Jaume García Villar and Climent Quintana-Domeque

Abstract

The problem of obesity is alarming public health authorities around the world. Therefore, it is important to study its determinants. In this paper, we explore the empirical relationship between household income and body mass index (BMI) in nine European Union countries. Our findings suggest that, in general, the association is negative for women and nonexistent for men. Moreover, once we decompose household income into “own labor earnings” and “other household income”, we find that the different relationship for men and women appears to be driven by the negative relationship between BMI and “own labor earnings” for women.

Link

Fat people are slow to react

HOMO - Journal of Comparative Human Biology doi:10.1016/j.jchb.2008.06.006

Relationship between simple reaction time and body mass index
Purchase the full-text article

A. Skurvydas et al.

Abstract

The aim was to establish the relationship between simple reaction time in motor response in young adults in relation to their body physique, as represented by body mass index. Forty-five young male participants were allocated to one of three anthropometric groups, based on their body mass index. Participants performed 100 reaction-time trials with instructions to move a joystick, as quickly as possible, as soon as they detected a single star appearing in the centre of a monitor. All data were statistically selected into seven intervals and data from the mode frequency interval were precisely analysed. Participants from the group with greater body mass index reacted significantly slower than others. We did not record group lateral differences based on simple reaction time in each selected group. We recommend for future researchers the importance of identification of the level of body mass index of participants prior to testing them for effectiveness of simple sensori-motor reactions.

Link

Social perception of obesity

Caption for figure:

1. Lean (L - narrow shoulders, thin torso and extremities, knee and elbow joints thicker than thy and arm diameter). 2. Muscular (M – Broad shoulders, curved extremities, chest and abdominal muscles shown, thy and arm diameters greater than knee and elbow joints). 3. Slightly fat and feminine (F – rounded shoulders, cylindrical extremities). Each of the three body forms was represented with (designated by +) and without (−) abdominal obesity as shown in rows. The sequence of these figures was randomized during the test and the figures were labeled serially by alphabets.

From the paper:

hysical characters were associated with the appropriate body forms as expected. The physical traits strong, rough and tough and physically aggressive were associated with the muscular non-obese [M−] figure. Lethargic was associated with F+. Disease prone was significantly associated with L− on the one hand and F+ on the other indicating that people negatively associate both the extremes with health. The trait swift was also strongly associated with L−. The traits that are not obviously physical were also strongly associated with certain body forms. Brave, conscious about looks, influential, dominating, status conscious, modern and confident were associated with M−; physical risk avoider, money minded, political, rich, stupid, selfish and greedy were associated most strongly with F+; friendly, intelligent, methodical, business risk avoider, successful, loving, kind, and honest were associated with F−; and L− was the commonest choice for swift, physical risk avoider, talkative and the trait depressed was associated with L+ [table 1].

Link to Table 1.

PLoS ONE doi: 10.1371/journal.pone.0003187

Obesity as a Perceived Social Signal

Manasee Mankar et al.

Abstract

Fat accumulation has been classically considered as a means of energy storage. Obese people are theorized as metabolically ‘thrifty’, saving energy during times of food abundance. However, recent research has highlighted many neuro-behavioral and social aspects of obesity, with a suggestion that obesity, abdominal obesity in particular, may have evolved as a social signal. We tested here whether body proportions, and abdominal obesity in particular, are perceived as signals revealing personality traits. Faceless drawings of three male body forms namely lean, muscular and feminine, each with and without abdominal obesity were shown in a randomized order to a group of 222 respondents. A list of 30 different adjectives or short descriptions of personality traits was given to each respondent and they were asked to allocate the most appropriate figure to each of them independently. The traits included those directly related to physique, those related to nature, attitude and moral character and also those related to social status. For 29 out of the 30 adjectives people consistently attributed specific body forms. Based on common choices, the 30 traits could be clustered into distinct ‘personalities’ which were strongly associated with particular body forms. A centrally obese figure was perceived as “lethargic, greedy, political, money-minded, selfish and rich”. The results show that body proportions are perceived to reflect personality traits and this raises the possibility that in addition to energy storage, social selection may have played some role in shaping the biology of obesity.

Link

Genes for Height and Body Mass Index; and, the limits of association studies

Quite often I find that the most interesting stuff in a paper isn't in its main content:

Simplistically speaking linkage studies are geared for relatively rare alleles with large effects within families (that may be of little effect in the population), whereas association studies are designed to detect common genetic effects that have smaller effects. In the case of rare monogenic disease, multiple rare variants at linked loci (allelic heterogeneity) seem to be the rule not the exception.42 For common polygenic disease and quantitative traits this question is still unanswered – there are examples for both common43 and rare alleles,44 and theoretical and empirical studies suggest a role for both rare and common variants.45

...

The modest LOD scores we observed for BMI despite the large study sample likely
reflects the heterogeneity of our study populations, and may suggest that there are relatively few common loci with strong effects for BMI across these populations.

This is a very important (and under-appreciated) issue. People have a genetic predisposition to be fat or thin; we are certain of as much. But what kinds of genes are responsible for this?

Under the "Common loci" explanation, in a population there is a limited number of genes which affect one's weight: if you get the "fat" genes you are likely to be fat, if you get the "thin" ones, you are likely to be thin.

An association study boils down to looking at people's genes and trying to correlate them with the trait of interest, e.g. their body mass index.

But, to discover such an association, people must be "fat" or "thin" because of the same genes. These genes must thus be "common" in the population.

If on the other hand, people are thin or fat because of family-specific genes, i.e. uncommon genes that are limited to families and are "uncommon" in the population, an association study can't detect them: it will notice that there are "fat" and "thin" people, but won't be able to find a common genetic pattern distinguishing the two.

A family-based linkage study, on the other hand, looks at the genes inherited by children from a parent. If, e.g. a fat father and thin mother have a fat daughter and a thin son, it pays off to see which genes were inherited by the daughter from the father: chances are, some of them may be the rare family-specific genes responsibly for her weight.

What this study has found is that rare rather than common loci are responsible for body mass index. In other words, people have a predisposition to be fat or thin mainly not because of genes that abound in the population, but because of rare genes common in a family.

If you have been paying attention in the last few years, you'd have noticed that genetic effects of discovered loci in association studies for quantitative traits have been rather underwhelming, explaining a very small (rarely more than 10%, usually less) percentage of the variation.

There are two reasons for this: first, many genes are responsible for each trait, but, more importantly, that a lot (in my opinion most) of the variation for quantitative traits is due to rare variants that can't be discovered by association studies.

The implications of this realization are manifold, but here are two:

• Companies such as 23andme and decodeme who offer personal genome scans aren't likely to offer any really interesting information to consumers any time soon. On the one hand, for legal reasons, they are unlikely to dabble into Mendelian traits that have big and dramatic effects on consumers' health. On the other, they can't figure out which particular family-inherited genes have a major impact on their customers' health (unless multiple family members get tested at several $100 each). Thus, they have to make do with the common alleles discovered in association studies that have minor effects. No wonder prices are dropping.
• Real progress will only come about with more developmental and functional studies, i.e. studies that actually look at what genes do in the body. Note, that in an association study, you don't really need to know what effect a particular allele has: if you discover a statistically significant correlation between its presence and a phenotype, you're done. But, to make progress, we have to understand how phenotypes are produced. Then, instead of estimating that a person will be obese because he carries particular gene found to have an association with obesity in population samples, we will be able to tell what effects the genes will actually have in his body. Naturally, this is easier said than done.

European Journal of Human Genetics doi: 10.1038/ejhg.2008.152

Genome-wide linkage screen for stature and body mass index in 3.032 families: evidence for sex- and population-specific genetic effects

Sampo Sammalisto et al.

Abstract

Stature (adult body height) and body mass index (BMI) have a strong genetic component explaining observed variation in human populations; however, identifying those genetic components has been extremely challenging. It seems obvious that sample size is a critical determinant for successful identification of quantitative trait loci (QTL) that underlie the genetic architecture of these polygenic traits. The inherent shared environment and known genetic relationships in family studies provide clear advantages for gene mapping over studies utilizing unrelated individuals. To these ends, we combined the genotype and phenotype data from four previously performed family-based genome-wide screens resulting in a sample of 9.371 individuals from 3.032 African-American and European-American families and performed variance-components linkage analyses for stature and BMI. To our knowledge, this study
represents the single largest family-based genome-wide linkage scan published for stature and BMI to date. This large study sample allowed us to pursue population- and sex-specific analyses as well. For stature, we found evidence for linkage in previously reported loci on 11q23, 12q12, 15q25 and 18q23, as well as 15q26 and 19q13, which have not been linked to stature previously. For BMI, we found evidence for two loci: one on 7q35 and another on 11q22, both of which have been previously linked to BMI in multiple populations. Our results show both the benefit of (1) combining data to maximize the sample size and (2) minimizing heterogeneity by analyzing subgroups where within-group variation can be reduced and suggest that the latter may be a more successful approach in genetic mapping.

Link

Mediterranean diet in Greco-Roman and Byzantine writers

Obes Surg. 2007 Jan;17(1):112-6.

Greco-Roman and Byzantine views on obesity.

Papavramidou N, Christopoulou-Aletra H.

This paper focuses on the Greco-Roman views on obesity with certain extensions to the Byzantine era. The writers reported hereby are Aulus Cornelius Celsus (circa 25 BC), Dioscorides Pedanius (40-90 AD), Soranus of Ephesus (98-138 AD) whose writings on the subject survived through Caelius Aurelianus (5th c. AD), Claudius Aelianus (3rd C. AD), Oribasius (324-400 AD), Aetius of Amida (circa 450 AD), Alexander Trallianus (6th c. AD), Paulus Aegineta (7th c. AD), and Theophilus Protospatharius (9th C. AD). All of the authors treat the subject of etiology, clinical manifestations and treatment, while the Hippocratic and Galenic views seem to be taken into consideration. The most important observation made on the basis of the studied texts is the emersion of the notion of the "Mediterranean diet" that was advised as an extremely successful conservative way to treat obesity. The Greco-Roman and Byzantine writers continue the long tradition of treating obesity and set the foundations for modern methods of treatment.

Link

Mismatch: Why Our World No Longer Fits Our Bodies

A new book which proposes that human health and lifespan will deteriorate because our bodies are no longer adapted in the increasingly foreign environment in which we find ourselves. I think that there is a three-way race between evolution, cultural change, and medical science. We may very well have sub-optimal genes for our modern environments, and evolution may not be able to catch up with the rates of cultural change, but medical science -by default- allows human beings to counterbalance our natural shortcomings. Until today, it has seemed to won the race, as increasing human lifespans indicate, but perhaps not into the future.

Here is a Guardian article on the book. An excerpt from the publisher:

We have built a world that no longer fits our bodies. Our genes - selected through our evolution - and the many processes by which our development is tuned within the womb, limit our capacity to adapt to the modern urban lifestyle. There is a mismatch. We are seeing the impact of this mismatch in the explosion of diabetes, heart disease and obesity. But it also has consequences in earlier puberty and old age.

Bringing together the latest scientific research in evolutionary biology, development, medicine, anthropology and ecology, Peter Gluckman and Mark Hanson, both leading medical scientists, argue that many of our problems as modern-day humans can be understood in terms of this fundamental and growing mismatch. It is an insight that we ignore at our peril.

Increase of weight in Greek schoolchildren in 20th century

Med Sci Monit. 2006 Dec 18;13(1):RA8-11 [Epub ahead of print]

The secular trend of body weight of Greek schoolchildren in the 20(th) century.

Papadimitriou A, Douros K, Fretzayas A, Nicolaidou P.

Background: Improvements in socioeconomic conditions in the 20(th) century had a dramatic impact on the growth and development of children, resulting in greater somatic growth and earlier pubertal maturation. Furthermore, in the last part of that century childhood obesity took on epidemic proportions in many countries The aim of the study was to present the secular trend of body weight of Greek schoolchildren in the 20(th) century. Material/Methods: The data were taken from growth studies the authors conducted themselves or were able to find in the Greek literature. All studies were cross-sectional and spanned the years from 1920 to 1995. The studies referred mainly to children living in Athens or other major cities of the country. Results: The data were taken from growth studies the authors conducted themselves or were able to find in the Greek literature. All studies were cross-sectional and spanned the years from 1920 to 1995. The studies referred mainly to children living in Athens or other major cities of the country. Conclusions: Improvement in the socioeconomic conditions in Greece resulted in an increase in body weight in Greek schoolchildren in the 20(th) century. However, this increase tended to stop in adolescent girls.

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Waist-hip ratio (WHR) not Body Mass Index (BMI) is a better predictor of mortality for the old

Waist-hip ratio should replace body mass index as indicator of mortality risk in older people (EurekAlert)

Older people with high waist-hip ratios (WHRs) have a higher mortality risk than those with a high body mass index, or BMI, a new study reveals.

Whereas justifiable attention is given to the increasing problem of obesity in the general population, far less is known about the relationship between obesity and mortality in older people, or how mortality risk should be estimated. The excess health risks associated with having a high BMI are known to decline with age, yet expert bodies such as the National Institutes of Health and the World Health Organisation have continued to use in older people the same BMI criteria as for other age groups.

Today's study, published in the American Journal of Clinical Nutrition, was carried out by a team based at the London School of Hygiene & Tropical Medicine. It sought to investigate the association of BMI, waist circumference (WC) and WHR with mortality and cause-specific mortality. The researchers studied 14,833 patients aged over 75 from 53 family practices in the UK; the subjects underwent a health assessment that included taking body measurements and a follow-up (with a median of 5.9 years) for mortality.

The findings confirmed that the current guidelines for BMI-based risk categories overestimate the risks of excess weight in people aged over 75 and are inappropriate for older men and women. This concurs with a previous study that found BMIs of 25-27 not to be a risk factor for all-cause and cardiovascular mortality in those aged 65 and over1. Most consistently, the data highlighted the risk of having a low BMI, with people in the lowest quintile (less than 23 in men and less than 22.3 in women) demonstrating the highest risk of death for total mortality and for major causes of death. Very underweight men (those with a BMI of under 18.5) were found to be particularly at risk.

'An explanation for the lack of a positive association with BMI and mortality at older ages is that, in older persons, BMI is a poor measure of body fat', say the authors. 'The measurement of weight does not differentiate between fat and fat-free mass, and fat-free mass (especially muscle) is progressively lost with increasing age

Waist circumference (WC) has been proposed as an alternate or additional measure of obesity. The study found no association with waist circumference and mortality. The authors continue: 'A limitation of WC alone as a measure is that it takes no account of body composition, whereas WHR is a measure of body shape and to some extent of lower trunk adiposity [abdominal fat]. Although it is possible theoretically for high WHR to coexist with thinness, our data show that those with high WHR had higher-than-average waist and average hip circumferences. We conclude that the association observed for WHR and mortality is probably explained by abdominal adiposity'.

The authors recommend that the current BMI-based health risk categories to define the burden of disease related to adult overweight and obesity be reviewed, as they are not appropriate for those over 75. They suggest that WHR should instead be used in this age group because of its positive relation with risk of death, and that attention should also be paid to the problem of underweight in old age.

Racial admixture, body mass index, and blood pressure

It is nice to see this article referring to "racial admixture" rather than one of the many euphemisms used to describe descent of individuals from two or more differentiated ancestral groups.

Human Genetics (Online first)

Racial admixture and its impact on BMI and blood pressure in African and Mexican Americans

Hua Tang et al.

Abstract Admixed populations such as African Americans and Hispanic Americans present both challenges and opportunities in genetic epidemiologic research. Because of variation in admixture levels among individuals, case-control association studies may be subject to stratification bias. On the other hand, admixed populations also present special opportunities both for examining the role of genetic and environmental factors for observed racial/ethnic differences, and for possibly mapping alleles that contribute to such differences. Here we examined the distribution and relationship of individual admixture (IA) estimates with BMI and three measures of blood pressure in two admixed populations in the NHLBI Family Blood Pressure Program (FBPP): African Americans and Mexican Americans. For the African Americans, we observed modest but significant differences in average African IA among four recruitment sites. We observed a slight excess of African IA among hypertensives compared to normotensives, and a positive (non-significant) regression of African IA on blood pressure in untreated participants. Within Mexican Americans, we found no difference in average IA between hypertensives and normotensives, but a positive (marginally significant) regression of African IA on diastolic blood pressure. We also observed a significant positive regression of Caucasian IA (and negative regression of Native American IA) on BMI. Our results are suggestive of genetic differences between Africans and non-Africans that influence blood pressure, but such effects are likely to be modest compared to environmental ones. Excess obesity among Native Americans compared to whites is not consistent with a simple genetic explanation.

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Rising obesity in Europe

This trend is documented in the IOTF media brief on obesity in the EU (pdf), and is especially worrying for the case of Greece (στα Ελληνικά). A related story:

At least U.S. has allies in coalition of the fat

March 16, 2005

BY JENNA PAYNE

BRUSSELS, Belgium -- At least seven European countries now challenge the United States in size -- at least around the waistline.

In a group of nations from Greece to Germany, the proportion of overweight or obese men is higher than in the United States, experts said Tuesday in a major analysis of expanding girth on the European continent.

''The time when obesity was thought to be a problem on the other side of the Atlantic has gone by,'' said Mars Di Bartolomeo, Luxembourg's Minister of Health.

In Cyprus, the Czech Republic, Finland, Germany, Greece, Malta and Slovakia, a higher percentage of men are obese or overweight than the estimated 67 percent of men in the United States, according to a report from the International Obesity Task Force.


Obesity is especially acute in Mediterranean countries, underscoring concerns that people in the southern region are turning away from the traditional diet of fish, fruits and vegetables to fast food high in fat and refined carbohydrates.

In Greece, for example, 38 percent of women are obese, compared with 34 percent in the United States, the group said.


Even in countries with low rates of obesity, troubling trends are emerging. In France, obesity in women and men is rising.

Stand up to lose weight

A new article in Science comes to the conclusion that lean individuals differ from obese ones in the amount of time they spent standing up. For a non-technical summary see The Fit Tend to Fidget, and Biology May Be Why, a Study Says and Why fidgeters tend to be leaner.

Science, Vol 307, Issue 5709, 584-586 , 28 January 2005

Interindividual Variation in Posture Allocation: Possible Role in Human Obesity

James A. Levine et al.

Obesity occurs when energy intake exceeds energy expenditure. Humans expend energy through purposeful exercise and through changes in posture and movement that are associated with the routines of daily life [called nonexercise activity thermogenesis (NEAT)]. To examine NEAT's role in obesity, we recruited 10 lean and 10 mildly obese sedentary volunteers and measured their body postures and movements every half-second for 10 days. Obese individuals were seated, on average, 2 hours longer per day than lean individuals. Posture allocation did not change when the obese individuals lost weight or when lean individuals gained weight, suggesting that it is biologically determined. If obese individuals adopted the NEAT-enhanced behaviors of their lean counterparts, they might expend an additional 350 calories (kcal) per day.

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Benefits of Mediterranean Diet

A new study from Europe in this morning's Journal of the American Medical Association shows just how powerful the effect of following healthy lifestyle advice can be over the years, reports The Early Show's Dr. Emily Senay.

Researchers looked at people aged 70 to 90 for more than a decade, and found those who adhered to a healthy low-fat Mediterranean-style diet lowered their risk of death by 23 percent. People who drank alcohol moderately lowered their risk by 22 percent. Physical activity lowered the risk by 37 percent. Nonsmoking lowered the death risk by 22 percent. And people who had all four of these healthy lifestyle factors lowered their risk of death from any cause by 65 percent.

It's powerful proof that a healthy lifestyle can work wonders.

The Mediterranean diet comes from countries like Italy and Greece. It's high in foods that provide health benefits like whole grains, fruits, vegetables, legumes, nuts, fish and olive oil.

It also includes low amounts of meat, dairy and saturated fats, and moderate alcohol consumption. Another new study showed that the Mediterranean diet reduced metabolic syndrome, a cluster of symptoms that puts people at a much higher risk for heart disease and Type 2 diabetes later in life like obesity, fat buildup in the arteries, high blood pressure, and glucose or blood sugar intolerance.

People on the Mediterranean diet had significant decreases in metabolic syndrome symptoms and risk factors and improvements in good cholesterol compared to those who weren't on the diet. There was also evidence that the healthier eaters suffered less from the inflammation of cells that may contribute to the risk of disease.

Two additional studies in the journal reinforce the importance of exercise in the health equation, even low-intensity exercise like walking. Physical activity was associated with better mental functioning in older women. Women aged 70 and older who participated in higher levels of physical activity scored better on cognitive performance tests and showed less cognitive decline than women who were less active.

A different study showed that even walking is associated with reduced risk of Alzheimer's in older men. Older men who walked the least had nearly twice the risk for diseases like Alzheimer's, compared to men who walked the most. This is the first time that a low-intensity exercise has been proven to keep the mind sharp.

Link (CBS)