June 18, 2013

Y-haplogroup I and cardiovascular risk

Arteriosclerosis, Thrombosis, and Vascular Biology. 2013; 33: 1722-1727

Male-Specific Region of the Y Chromosome and Cardiovascular Risk Phylogenetic Analysis and Gene Expression Studies

Lisa D.S. Bloomer et al.

Abstract

Objective—Haplogroup I of male-specific region of the human Y chromosome is associated with 50% increased risk of coronary artery disease. It is not clear to what extent conventional cardiovascular risk factors and genes of the male-specific region may explain this association.

Approach and Results—A total of 1988 biologically unrelated men from 4 white European populations were genotyped using 11 Y chromosome single nucleotide polymorphisms and classified into 13 most common European haplogroups. Approximately 75% to 93% of the haplotypic variation of the Y chromosome in all cohorts was attributable to I, R1a, and R1b1b2 lineages. None of traditional cardiovascular risk factors, including body mass index, blood pressures, lipids, glucose, C-reactive protein, creatinine, and insulin resistance, was associated with haplogroup I of the Y chromosome in the joint inverse variance meta-analysis. Fourteen of 15 ubiquitous single-copy genes of the male-specific region were expressed in human macrophages. When compared with men with other haplogroups, carriers of haplogroup I had ≈0.61- and 0.64-fold lower expression of ubiquitously transcribed tetratricopeptide repeat, Y-linked gene (UTY) and protein kinase, Y-linked, pseudogene (PRKY) in macrophages (P=0.0001 and P=0.002, respectively).

Conclusions—Coronary artery disease predisposing haplogroup I of the Y chromosome is associated with downregulation of UTY and PRKY genes in macrophages but not with conventional cardiovascular risk factors.

Link

10 comments:

mooreisbetter said...

OK, let me state the obvious:

Most "I" populations are still native Scandinavians or native SW Slavs (Croatians, etc.) with little admixture.

Might this be a correlations without causation? Might the autosomes of those populations have something to do with it?

The only way to confirm if this is indeed sex-linked, and if it is indeed linked to M170 (Hg I), would be to test the random, oddly distributed Hg I clades, like M26-Sardinia and the British Isles clades and see if the patterns hold true.

Sardinians have the lowest rates of these diseases in the world, outside Japan.

An even better way to test these would be to test people descended from one I ancestor on the male line but thoroughly admixed. For example, someone whose great-great grandfather was Swedish I but who the rest of the heritage was Japanese or whatever. Then they are testing for male sex-linked, and not just testing populations!

Put in the simplest possible terms, statements like this are not logically sound:

--Africa is populated by HGs A, B, and E.

--People of HG A, B, and E tend to die early.

--Therefore, there could be a male sex-linked gene for premature death.

No. This totally ignores other factors in the geographical locale of the modern Hg distribution.

CarolAST said...

I could only find one study claiming that haplogroup I was associated with cardiovascular disease, and it included only British men. That study admitted they had no data on whether men with haplogroup I were over-represented in areas with higher rates of heart disease.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314981/

So, their hypothesis shouldn't be regarded as solid in the first place. As for this study, it only claimed that "haplogroup I of the Y chromosome is associated with downregulation of UTY and PRKY genes in macrophages," but neither they nor others have established that those genes are associated with heart disease.

matt said...

Here is a report on higher Aids mortality for haploid group I males.

http://dienekes.blogspot.com/2010/06/y-chromosome-haplogroup-i-and-disease.html

No doubt some researcher will do a study on I-haploid group males and their sisters mortality from things like Cystic Fibrosis etc, visa vi other haploid group males and their sisters.

Grognard said...

moore, they compare it to people of the same areas with other Y DNA types and they have a mechanism of why this would be so.

Very interesting because the more pressure there exists for selection on what are generally treated as neutral markers, the less valid they are. Also things like molecular clock go out the window if there's selection on Y DNA or mt DNA and there's good reason to think that there is. Especially on mtDNA which is pretty important to your health at a basic cellular level.

Grey said...

"Might this be a correlations without causation?"

It's still an interesting clue precisely because of the non-random geography.

Dr Rob said...

Lets not forget the high pork Balkan diet. Don't know what they eat in Scandinavia - Turnips ? (Joke)

Grognard said...

Also if you wonder why generally people in higher altitudes live longer and have less heart disease google "brisket disease" or "the old black breed".

For cattle high altitude deaths are a serious problem and can be a problem for humans as well. That's why some people get bad altitude sickness and others barely notice, doubtless this is selected on pretty heavily if you live in an area it matters.

eurologist said...

Most "I" populations are still native Scandinavians or native SW Slavs (Croatians, etc.) with little admixture.

mooreisbetter,

My guess is that the largest population of I-carriers are Germans, since I makes up 20-30% of the male population in a central strip running down Germany. And, given the ubiquity of different male and female haplotypes, history/ archaeology, and the Central European location, it is fair to say that Germans are rather well admixed.

I read the abstract like they think they have found a causative effect, but I don't think they have proven much, if anything.

Charlotte said...

Here's a hypothesis: Suppose that (and it's a big "if") the men among the bearers of the Ertebølle culture were predominantly Y-haplogroup I. Ertebølle people ate an enormous amount of cold-water, fatty fish, loaded with Omega-3. This diet would have protected them against cardiovascular disease, perhaps sufficiently that genetic protections might have been lost. When the Ertebølle people switched to farming and animal husbandry, their diet would no longer have protected them against cardiovascular disease, and they would now be at elevated risk.

I have a dog in this fight: the men in my family are haplogroup I, and as for cardiovascular disease among them -- can we talk?

Grognard said...

mt DNA and Y DNA seem to be tied to strong selection based on diet. It's not implausible at all but impossible to be certain of.