November 05, 2012

GWAS study of pigmentation in four European countries

From the paper:
Males (M) have consistently lighter pigmentation (lower scored) than females (F) in all four countries. Among countries, the largest pigmentation difference is with Ireland, where, in our sample, individuals have lighter pigmentation or lower M index on average than in Poland, Italy, or Portugal. Hair pigmentation histogram (C) and boxplot by country (D) in 341 individuals showing the distribution of hair pigmentation and the differences among countries. In our sample, individuals from Northern European countries (Ireland, Poland) have on average lighter hair pigmentation than individuals from Southern European countries (Italy, Portugal). The distributions in males are similar to those in females in all countries except Ireland, where, in our sample, males have darker hair color than females (not shown). Eye pigmentation histogram (E) and boxplot by country (F) in 468 individuals showing the bimodal distribution of eye pigmentation and the differences among countries. Comparison with self-reported phenotypes shows that the two modes of the distribution correspond to blue and brown eye color, while individuals reporting green and hazel eye color have intermediate C’ values. As with hair pigmentation, in our sample, individuals from Northern European countries have on average lighter eye pigmentation than individuals from Southern European countries. 
Interestingly, our analysis of variation in skin color in Europe demonstrates a consistent difference in skin color between the sexes. By the DermaSpectrometer M index measure, males are more lightly pigmented than females in each of the four European countries we studied. The same trend in M index was reported previously in a sample of European Americans [38]. Our results in populations of European ancestry contradict earlier anthropological studies that have concluded females are more lightly pigmented than males in most populations (reviewed in [2]). One potential reason for the conflicting results is the different instruments used. In early studies, which used the Evans Electric Limited (EEL) and Photovolt broad-spectrum spectrophotometers, skin pigmentation estimates may be confounded by the hemoglobin level to a greater extent than for the DermaSpectrometer used in the present study [46].

Some data (lower = lighter):

One thing of interest is that while Irish males/females are both lighter-eyed than other Europeans, including Poles from northern Europe, Irish females appear to be lighter-haired than Irish males (96.3 vs. 106.7), but no such substantial sex difference exists in the Poles in this trait (107.5 vs. 109.5). Sexual dimorphism seems to lean in the direction of lighter male skins and lighter female hair across the four countries.

Peter Frost has offered the theory that "gentlemen prefer blondes" because during the Ice Age boreal hunters lived a harsh lifestyle that killed many of them, but the remainder could not adopt a polygynous lifestyle, because provisioning for a wife was expensive. As a result, women had to compete for the remaining men, and men could be picky, preferring those with a "rare color advantage." It is not immediately clear to me how this might explain the Ireland vs. Poland differentiation, assuming it reflects a broader NW/NE trend, since NE Europeans are more likely to be descended from hunter-gatherers of the tundra-steppe.

PLoS ONE 7(10): e48294. doi:10.1371/journal.pone.0048294

Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations

Sophie I. Candille et al.

Pigmentation of the skin, hair, and eyes varies both within and between human populations. Identifying the genes and alleles underlying this variation has been the goal of many candidate gene and several genome-wide association studies (GWAS). Most GWAS for pigmentary traits to date have been based on subjective phenotypes using categorical scales. But skin, hair, and eye pigmentation vary continuously. Here, we seek to characterize quantitative variation in these traits objectively and accurately and to determine their genetic basis. Objective and quantitative measures of skin, hair, and eye color were made using reflectance or digital spectroscopy in Europeans from Ireland, Poland, Italy, and Portugal. A GWAS was conducted for the three quantitative pigmentation phenotypes in 176 women across 313,763 SNP loci, and replication of the most significant associations was attempted in a sample of 294 European men and women from the same countries. We find that the pigmentation phenotypes are highly stratified along axes of European genetic differentiation. The country of sampling explains approximately 35% of the variation in skin pigmentation, 31% of the variation in hair pigmentation, and 40% of the variation in eye pigmentation. All three quantitative phenotypes are correlated with each other. In our two-stage association study, we reproduce the association of rs1667394 at the OCA2/HERC2 locus with eye color but we do not identify new genetic determinants of skin and hair pigmentation supporting the lack of major genes affecting skin and hair color variation within Europe and suggesting that not only careful phenotyping but also larger cohorts are required to understand the genetic architecture of these complex quantitative traits. Interestingly, we also see that in each of these four populations, men are more lightly pigmented in the unexposed skin of the inner arm than women, a fact that is underappreciated and may vary across the world.



truth said...

Nice. It was about time to get a study on pigmentation, using SNPs and with plots and such. As I expected the Portuguese are ligther skinned and blonder than Italians, but less fair-eyed.
A shame there are only 4 populations.

shenandoah said...

"Peter Frost has offered the theory that "gentlemen prefer blondes" because during the Ice Age boreal hunters lived a harsh lifestyle that killed many of them, but the remainder could not adopt a polygynous lifestyle, because provisioning for a wife was expensive. As a result, women had to compete for the remaining men, and men could be picky, preferring those with a "rare color advantage."

Lol, what a fantasy.

"provisioning for a wife was expensive" -- as if women didn't work hard then as always. Women did most of the ~dirty work, in fact (as always).

"...women had to compete for the remaining men, and men could be picky..."

LMAO. Those men were indeed polygynous, but they did like unusual coloring and looks. They also preferred submissive, dumb women -- then, as now.

Matt said...

Re:dimorphism. The skin color difference is interesting. I think the way the paper phrases it is more nuanced than "men have lighter skin in these populations" (I'm paraphrasing you with less justice than you paraphrase the paper here, of course):

"Interestingly, we also see that in each of these four populations, men are more lightly pigmented in the unexposed skin of the inner arm than women, a fact that is underappreciated and may vary across the world.".

It's a lot easier for me to believe that the inner arm skin, which is not really very exposed to either sunlight or the human gaze, compared to say the face, might kind of random walk very slowly in its pigmentation between men and women, so that it by chance tends to be lighter in men in Europe, than that all the facial composites involving these populations which showing lighter facial skin in women (although there is a "less ruddiness" component at work there as well) are wrong... The inner arm skin is not just "unexposed" after all - it is "on the inner arm", and thus unexposed not just by chance but across its specific evolutionary history.

The Ireland vs Poland discrepancy is also interesting. Certainly it seems from this that Irish are lighter than would be expected from, say, an admixture of present day Spanish/Sardinian & Lithuanian which would produce the same level of "Mediterranean" and "North European" components (to use the components you have found), presuming the Lithuanians are not much more lightly pigmented than the Polish. Whatever the actual evolutionary history of the Irish (whether it actually is an admixture like situation like this or not).

It seems hard to square this with the idea that all present day populations are admixtures of various components, which were real populations at some time, and that pigmentation evolution all happened before this hypothetical admixture (the logical interpretation of combing Frost's theory on pigment evolution with your theories on ancient population structure).

apostateimpressions said...

I would guess that HGs varied in pigmentation were there less adequate food sources of Vatican D in some parts. There may also have been climatic differences, some parts cloudy or colder. Just a guess...

andrew said...

The most plausible explanation at first blush would be that light skinned people (Vikings?) in some wave or other of migration introgressed in a male biased way into a darker skinned population and that factors like linkage have maintained that bias at a low level today.

eurologist said...

IIRC previous studies have shown that European men look darker than women due to increased presence of subcutaneous blood, whereas this study solely looks at pigmentation.

Because of the vital Vitamin D and folic acid balance, I am sure selection on skin pigmentation is substantial over just a few hundred generations (while populations with high vitamin D intake can be darker than expected); hair color less so, and I am thinking eye color is mostly an unintentional side effect (although light eye color might very well be selected against in the south).

And from my experience, Lithuanians are quite a bit fairer than Poles.

Anonymous said...

You notice that with children. The children with the white blond hair and deep blue eyes tend to be male. In adults the females tend to artificially lighten their hair beyond the level when their hair was at its fairest. I never appreciated Mr. Frost's ideas, though it is true for some non European groups that the males are darker skinned than the females but that is due to the males preferring a more outdoor life. In Australia you frequently see East and Southeast Asian women (Chinese, Vietnamese) fully clothed with hat and gloves when outdoors in the sun. They look rather odd in their winter garb in summer but vanity makes people do odd things.

In my ethnic group, blue/grey/green eyes have no correlation with skin tone or hair color.

Crimson Guard said...

Hooton had a theory on the Irish eye color peculiarities. Brown eyes are commoner among Irish females. I've posted information on the physical anthropology of the Irish over at AS during the past year:

"The residue of "Pure Mediterraneans," being much larger than that of the "Pure Alpines," suggests that these long-headed, dark-haired, dark-eyed people may have been much more numerous in that color combination in Ireland in ancient and prehistoric times than were ever the Alpines. Such Pure-Mediterranean types are apparently far more common today in Wales, Scotland, and in England than in Ireland."

"Pure dark eyes are supposedly dominate over light eyes in Mendelian inheritance, although this matter is not as simple as it once seemed. However, if there had been at some time or other, a ponderable proportion of dark-eyed people in the Irish population - say from 25 to 50 % - apart from selective factors operating against the survival of dark-eyes persons, we should expect that dark eyes would occur by Mendelian recombination in the mixed descendants in at least 12 1/2 to 25 %. But if the dark-eyed persons always constituted a very small minority - say 5 to 10 % - it is conceivable that they would disappear entirely by accidental gene loss(the phenomenon known as "genetic drift"). Such a disappearance could occur if the the few dark eyed persons were dispersed in an overwhelming majority of light-eyed individuals. This would make an excellent explanation of the virtual absence of dark eyes in Ireland if we could suppose that the various immigrant stocks included very few with dark eyes. In consideration of the fairly high frequency of dark eyes in the population of Britain, which to a great extent is supposed to be the source of the Irish colonization-Mesolithic, Neolithic, Iron Age, and historic-it is hardly conceivable that there were not many waves of immigrants which included very substantial proportions of persons with dark eyes.

It therefore seems that the evidence of selective survival of light-eyed persons and of progressive elimination of dark-eyed persons throughout the older age groups may afford us the best clue to a solution of the problem. Of course, this explanation raises the presumption that most of the dark-eyed Irish either die early in life or marry light-eyed mates and leave only mixed-eyed progeny. (In this connection there should be introduced data having to do with the percentage of dark eyes in Irish females. Our recollection of the Dawson material is that they are considerably more common.)"

--The physical anthropology of Ireland: by Earnest Albert Hooton, Clarence Wesley Dupertuis, Helen Dawson , 1955

Fanty said...

It also doesnt correlate to 1950s ideas of hair/eyes pigmentation, wich saw for both the baltic sea as the center (with Swedes, Finn, Baltic states, North-Poland, Northeast Germany and Denmark as the least pigmented (hair and eye wise) region of the world.

And this map here:

is an average from 3 maps originaly showed on the Eurogenes blog. Wich showed the frequencies of 3 hair and eye color related SNP in Eurogenes project members

As far as I recall, the actual percentages had been highest in Lithuanians and lowest in Sardinians (not shown here on the map, but the creator of the maps said so) Sardinia had less light pigment SNP than Spain or even Turkey.

Davidski said...

^ Fanty, these Candille et al. results need to be replicated with larger samples, because they look a bit off IMO. Maybe Ireland should be divided into regions...and in fact so should all the countries.

AndyC said...

According to the Facial Hair Conjecture, you would expect for northern latitude populations during the winter months only the face would be exposed to the sun. Men with significant facial hair would have less Vitamin D producing skin exposed to the sun compared to women. Therefore there would be stronger selection for light pigmentation in hairy northern latitude men. For a northern latitude population with less facial hair (Inuit?), you would expect less difference between the sexes.

AWood said...

From my past experiences, people of my background are the lightest by far. It's not surprise that ruddy skin (hardly any pigment at all) is most common in Ireland and likely UK (if it was studied) too.

To an above poster, hardly a result of alleged, often fictitious vikings. We've always been the most depigmented with or without invasions. Do not confuse blonde hair and blue eyes with ruddy/depigmented skin with which there is no correlation.

Anonymous said...

All these are not statistically significant. If there is an effect it has to be hormonal. An inheritable facter whould have to be on the sex chromosomes, which seems unlikely.

Plus this just does not match my experience which is men tend to have darker skin simply because they spend more time outdoors.

I am consigning this to the dodgy basket.

pconroy said...

I'm Irish, grew up in Ireland,and these results tally well with my own experience.

My father is typical as he has a somewhat Mediterranean look, but has black/brown hair, blue eyes and fair complexion - - think Daniel Day-Lewis.

I have green eyes, can not tan at all, black/brown hair.

pconroy said...

As regards Vikings being fairer skinned than Irish - very unlikely. Fairer haired probably, but not skin. Most Scandinavian can tan, and many can tan well - most Irish tan poorly or not at all - like me.

eurologist said...

All these are not statistically significant. If there is an effect it has to be hormonal. An inheritable facter whould have to be on the sex chromosomes, which seems unlikely.

There could be epigenomic factors - but I agree: skin smoothness, thickness, and hair follicle density and hair thickness already seem controlled by sex hormones - so there is a good chance, this explains such minor pigmentation dimorphism expressions, as well (and don't forget the difference between the skin proper and subcutaneous blood).

I was tempted but didn't want to bring up Daniel Day-Lewis, but I agree you can see that along the shore and also in Norway and western Sweden: a higher dark hair:blue eye or light skin ratio than what you would expect. In fact, such ratios may be better discriminators and should be tallied.

I also agree that the tanning ability should be another hugely important component, since it is a significant adaptation to large seasonal variability.

Katharós said...

A interesting aspect of vitamin D3 "Cholecalciferol" deficiency and women is the inflammatory disease Multiple sclerosis, which is more common among white Women especially in the northern hemisphere. There are a lot of studies that link decreased sunlight exposure as one of the outbreak causes of MS.

Tobus said...

@AnnieMouse: Plus this just does not match my experience which is men tend to have darker skin simply because they spend more time outdoors.

That's why they sample from the inner arm - so environmental effects won't skew the results.

Justin said...

Pontos' post is right on: it was apparent to me years ago that males were of lighter complexion than females just from pure observation, and I found it odd how people would always quote some research saying that females were lighter with total conviction despite how it should betray their "empirical eyes" - but, you'd have to Really look at men! :o I knew time would reveal the truth, but it was disheartening to see how much people's "objectivity" was colored (ooh pun, wow!) by anecdotes or idioms (the fairer sex), and glaring oversights: like wearing make-up all the time, dolled-up photos (lighting: pretenses like making people look fair or 'brighter') and hair dye, and "natural" hair lightening from sun-damage, or shampoo, that more affects longer hair, as it hasn't been cut off in a while. Also, anyone ever notice how most of the people with naturally orange hair as adults are men??

apostateimpressions said...

It looks like I wasnt far wrong.

But according to researchers, Britain may be the most red-headed part of the world simply because it gets more cloud than Scandinavia because of its maritime climate. In Sweden, the average daily number of sunshine hours is 5.4, while in Scotland it is 3.1.

Blogeditor said...

So what exactly is the percentage breakdown here? Sorry if the answer is obvious.