July 23, 2015

Diversity is (very slightly) good for you

This isn’t in the local news, but there are stories about it in the world media: a new paper in Nature on associations between genetic diversity and various desirable characteristics.  I’m one of the authors — and so is pretty much everyone else, since this research combines analyses from over 100 cohort studies.  The Nature paper is actually the second publication in this area that I’ve worked on.  My first Auckland MSc student in Statistics, Anish Scaria, did some analysis for a different definition of genetic diversity, and that plus data from a smaller group of cohort studies was published last year.

What did we do? Humans, like most animals and many plants1, have two copies of our complete genome2. We looked at how similar these two copies were, essentially measuring small amounts of inbreeding from distant ancestors.

Each cohort study had measured a large number of binary genetic variants, ranging from 300,000 to 1,000,000. In the first paper we looked at just the proportion of variants where the two copies were the same3. In the new paper we looked at contiguous chunks of genome where all the variants were the same in the two copies, which gives a more sensitive indication of the chunks of genome being inherited from the same distant ancestor. We compared people based on the proportion of genome that was in these contiguous chunks.

The comparisons were done separately within each cohort and the associations were then averaged: obviously you would get different genetic diversity in a cohort from Iceland versus a cohort of African-Americans, and we need to make sure that sort of difference didn’t get incorporated in the analysis. Similarly, for cohorts that recruited people of different ancestries, the comparisons were done between people of the same basic ancestry and averaged.

Our first paper found that people with more difference between their two genomic copies lived (very slightly) longer on average; the new paper found that (to a very small extent) they were taller, had higher average scores on IQ tests, and had lower cholesterol. The basic direction of the results wasn’t surprising, but the lack of association for specific diseases and risk factors was — there was no sign of a difference in diabetes, for example.

Scientifically, the data provide a little bit of extra support for height and whatever IQ tests measure having been under evolutionary selection, and a bit of negative evidence on diabetes and heart disease having been under evolutionary selection in human history. And also a bit of support for the idea that you can actually get more than a hundred groups of independent and fiercely territorial academics to work together sometimes.

 

 

1. Some important crop plants, such as wheat, cabbage, and sugarcane, are insanely more complicated
2. Yes, I’m ignoring the sex chromosomes here.
3. “Homozygous” is the technical term.

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Thomas Lumley (@tslumley) is Professor of Biostatistics at the University of Auckland. His research interests include semiparametric models, survey sampling, statistical computing, foundations of statistics, and whatever methodological problems his medical collaborators come up with. He also blogs at Biased and Inefficient See all posts by Thomas Lumley »

Comments

  • avatar
    Steve Curtis

    Im not sure after choosing 16 health related traits, some of which seem very general such as educational attainment, that this is then related to homozgosity ?

    While i’d never heard of this technical term, checking it out briefly, it does come into play for specific genetic conditions like cystic fibrosis, the parents both being Heterozygous, the child is then ‘matched’, with one copy from each parent.

    Do they actually have the specific genes for height much less the genes for education achievement. In individuals we can measure height and IQ so you can put them in different groups and I accept if you have one taller parents their children are taller, but this study doesnt connect groups of taller parents or grandparents with their offspring. The IQ one seems fraught with difficulty as there is no data for distant ancestors .

    9 years ago

    • avatar
      Thomas Lumley

      Height unquestionably has a major genetic component, from many genes, quite a few of which are known.

      The evidence is less strong for IQ, but the fact that studies of nearly unrelated people give similar heritability estimates to studies of family members does provide some evidence that the family study results aren’t totally bogus. Again, some specific genes are known, but there is evidence for a lot of unknown genes.

      Conditions like cystic fibrosis and sickle-cell disease are a bit different. (Pre)historically, carrying a single copy of the disease variant must have had some benefit, otherwise the disease would have been wiped out over time because of the devastating effects of carrying two copies.

      For sickle-cell we know exactly what the benefit is, and even the molecular mechanisms: carrying one copy protects you from malaria.

      For cystic fibrosis the evidence is less solid, but the same genetic defect in rats protects against typhoid fever.

      “Directional dominance”, or a non-additive effect of the two copies of the genome is less well understood, but it is thought to indicate traits that are under evolutionary selection. Undesirable mutations that have some effect when one copy is present will be removed more rapidly than undesirable mutations that only have an effect when two copies are present. One reason the argument is weaker than for cystic fibrosis and sickle-cell is that most human genetic variation is quite recent, making it hard to tell how much selection should have occurred.

      Even so, the data provide a small bit of supporting evidence — and that’s what most progress in science is like.

      9 years ago

  • avatar
    Megan Pledger

    Congrats on the Nature publication.

    9 years ago