August 28, 2010

Y-chromosome haplogroup I and heart disease

There was a recent study on AIDS progression and Y-chromosome haplogroups. There is a new one on haplogroup I and coronary heart disease. I haven't tracked down the article yet, but here is the press release from the European Society of Cardiology:
Scientists in the UK have shown that genetic variations in the Y chromosome affect a male’s risk of coronary heart disease. It is well known that males have a higher incidence of coronary heart disease than females due, in part, to the Y chromosome they inherit from their fathers. To investigate the role of the Y chromosome further, a team from the University of Leicester carried out research to determine whether genetic variations in the Y-chromosome affect risk for males.

Not all Y chromosomes are the same. There are variants within the male gender called “Y-haplogroups”, which are usually associated with specific geographic regions and tend to indicate the origin of the ancestral line. Professor Nilesh Samani explains the background to the project that was funded by the British Heart Foundation, “We set out to determine if men with differing types of Y chromosome were at differing risk of heart disease. We tested nearly 3,000 British males, and found that those carrying the I-haplogroup variant had a 55 percent higher risk of coronary heart disease.”

Of the 3,000 men tested, 1,295 were the cohort group of those with coronary heart disease and the rest were the control group. The Y-haplogroup was identified in all men, and the results showed that those in the I-haplogroup had an approximately 55 percent higher risk of coronary heart disease compared to the others. The association of the I-haplogroup with coronary heart disease was independent of, and not explained by, traditional heart risk factors such as cholesterol, high blood pressure and smoking.

Commonly found in central, eastern and northern Europe, the I-haplogroup is carried by about 13 percent of British men. Its origin is thought to be of the Gravettian culture, which arrived in Europe from the Middle East about 25,000 years ago. Since the I-haplogroup is not so prevalent in southern parts of Europe, an interesting speculation is whether it contributes to the higher levels of coronary heart disease in the north compared to the south – however, this requires further research and testing.

What is clear from this study though, is that men carrying the I-haplogroup are more likely to suffer from coronary heart disease than men with other Y-haplogroups.


Gioiello said...

It would be interesting to understand why and it shouldn't be difficult: some known or unknown SNP which mutates some gene and, if it is worth for the whole haplogroup, a very ancient SNP, which is at the origin of the haplogroup. Not difficult, likely.
Probably in the paper of Rozen et alii there could be an answer.

aargiedude said...

I-haplogroup had an approximately 55 percent higher risk

I-haplogroup is carried by about 13 percent of British men

Wrong. Capelli's 2003 study of Britain found 18% y-dna I in England, Wales, and Scotland. I found 21% y-dna I in England and Wales. That's 20% total, with a sample size of 5,000.

Now guess what? That's 55% greater than the 13% frequency the study is claiming. I wonder if that's the reason they believe y-dna I is over-represented in the heart disease samples.

Anyhow, even if I'm wrong on this particular case, these kinds of studies just don't pass the statistical quality test. One of the haplogroups will inevitably have a distorted frequency, unless you sample maybe 10,000 people. Worse are the association studies that look at autosomal dna. With hundreds of thousands of SNPs, it's almost guaranteed you will find at least one that has a near perfect correlation with any randomly selected set of samples.


There are a few genes on the y-chromosome, right? So presumably, if a gene is added/lost/altered it would be sort of like an SNP event, occuring at a specific point on the y-dna tree. Has there been any study to see if there are differences in the y-chromosome genes, and if so, associate them with y-dna haplogroups?

aargiedude said...

From Jobling (2009), a study of British surnames and their associated y-dna haplogroups:

427 I
1793 total samples

24% y-dna I

Gioiello said...

Argiedude, I think that these studies are calculated upon the percentage of the person tested and not on the percentage of the population they don't know. Anyway these studies are above all statistical, like deCODEme and 23andME. Anyway they "ci chiappano", "c'azzeccano" would say Di Pietro: hit the mark.

Anonymous said...

Somewhat related: I've been wondering what the genetic reason for Southern Europeans having much lower rates of lung cancer than Northerners. Like the Japanese, it seems they can smoke quite a lot and still have fairly low chances of getting lung cancer, while Northern Europeans and Africans run a much higher risk.

I presume this has something to do with earlier urbanization of their populations, living in warmer places with worse air.

Gioiello said...

Erranter, who did 23andMe does know why: there is a mutation that cause the lung cancer by smoke: who has it has also difficulty to not smoke, who hasn't finds very easy not smoking or stopping to smoke and smoke probably wouldn't cause him cancer.

I haven't it and I don't smoke.
Double defense.

Anonymous said...

You shouldn't put too much faith in those haplogroup studies which use such small groups to represent an entire nation comprising millions of people. They don't really hold water statistically, but are just crude estimates.

There are other reasons for men of haplogroup I in the UK having more heart disease, and I am sure it has absolutely nothing to do with a tiny bit of useless dna that encodes their haplogroup on nearly useless chromosome. Keep researching and find the real causes, and not coming up with silly excuses.

Andrew Oh-Willeke said...

"I-haplogroup had an approximately 55 percent higher risk

I-haplogroup is carried by about 13 percent of British men

Wrong. Capelli's 2003 study of Britain found 18% y-dna I in England, Wales, and Scotland. I found 21% y-dna I in England and Wales. That's 20% total, with a sample size of 5,000."

This doesn't affect the conclusion for a study with this methodology. The study looked at the rate of cardiac problems in each Y haplotype subgroup of the sample. So long as the cardiac disease rate is statistically significant in each Y haplotype subgroup, it doesn't matter if the proportion of people in each subgroup is in line with the national average.

When the difference is 55% in prevalence rate, in a condition found in 40% of the sample, the haplogroup sub-samples don't have to be all that large to have unequivocal statistical significance. The more impact a genetic trait has on a relatively common phenotype, the smaller the sample you need to detect it.

"There are other reasons for men of haplogroup I in the UK having more heart disease, and I am sure it has absolutely nothing to do with a tiny bit of useless dna that encodes their haplogroup on nearly useless chromosome."

The existence of a Y chromosome genetic component to cardiac risk has already been demonstrated in previous research on hereditary causes of cardiac risk involving much larger sample sizes. The most important environmental risk factors have also been directly controlled for in the study.

The study doesn't speculate on a mechanism, but it certainly wouldn't be surprising if the risk factor that is showing up in the heart disease data has something to do with Y-DNA controlled testosterone system via the stress that testosterone induced emotional reactions impose on the heart, for example, so there are plausible mechanisms by which a mutation in the Y-DNA of a significant share of Y-DNA in haplotype I men could impact cardiac disease risk.

Since Y-DNA haplogroup is a fairly invisible trait, and the population of white British men has not seen much profound migration in the last thousand years and all have access to the national heath care system, the case that Y-DNA haplotype I is a proxy for some environmental effect related to population structure among white British men seems less likely than it would be in other societies. It can be definitely ruled out, but since most known migrations into Britain have involved more than one haplotype, it would be quite surprising to see the legacy of that kind of population structure driven environmental effect confined to a single Y-DNA haplotype, rather than to a cluster of two or three haplotype groups associated, for example, with pre-Norman populations.

Certainly, the particular mutations that used to actually define the I-haplotype don't have to be the cause. But, the study makes a good case that a Y chromosome mutation that gives rise to cardiac risk is a fellow traveler of the mutations that define the I-haplotype (or at least some of its common subtypes).

Further, you don't have to know the precise frequency of Y-DNA haplotype I in the British or Northern European population to conclude that it is more common in Central, Eastern and Northern Europe than it is in Southern Europe, as long as the difference in frequency is not slight, which would in turn support investigation of the hypothesis that this could partially account for regional differences in heart disease rates.

Unknown said...


Thanks for the very interesting blog and for this find!

There is a paradigm which you may want to consider, though it does not fit very well with the estabished dogma of Neolithic transition as progress in postives sense. There is evidence that human health suffered tremendously as a result of switching to a grain-based diet. (Agriculture was also associated with the origin of slavery). After all, there are reasons for the myth of the first humans being expelled from Eden to farm the soil and reproduce in pain (narrowed birth canal due to bone demineralisation). Perhaps Gobekli Tepe will tell us more...

In any case, it is likely, that populations which were exposed to grains for more generations, managed to get used to them to some extent. This would not be the case with the "autochtonous" mesolithic hunters-gatherers of northern and eastern Europe, or with the Gravettian I haplogroup.

I recommend looking at Lutz:

Ashton said...

Hi. I just found out I'm Haplogroup I2a Y Chromosome. All my Paternal male-line has been based in Yorkshire, England as far back as anyone can trace, and Brooks was the original surname. As it is not so common there, does anyone have any ideas as to its' oorigins in England, where I see it occurs at only 1%-3%?? From my research, it doesn't look at all Viking nor Anglo-Saxon nor Briton. Help, very appreciated.