john hawks weblog

paleoanthropology, genetics and evolution

type 2 diabetes

  • Stopping the study

    Sun, 2012-10-21 11:05 -- John Hawks

    Gina Kolata reports on a surprising result for a long-term study of diet and exercise in the treatment of type 2 diabetes: "Diabetes Study Ends Early With a Surprising Result".

    The study randomly assigned 5,145 overweight or obese people with Type 2 diabetes to either a rigorous diet and exercise regimen or to sessions in which they got general health information. The diet involved 1,200 to 1,500 calories a day for those weighing less than 250 pounds and 1,500 to 1,800 calories a day for those weighing more. The exercise program was at least 175 minutes a week of moderate exercise.

    But 11 years after the study began, researchers concluded it was futile to continue — the two groups had nearly identical rates of heart attacks, strokes and cardiovascular deaths.

    One expert quoted in the article thinks that the large effects of smoking cessation, statin drugs and blood pressure medications may swamp the small effect of diet and exercise. Swamp the small effect of diet and exercise on type 2 diabetes in obese patients? Wow.

    Tags: 
    type 2 diabetes
    health

  • The risk gradient

    Wed, 2011-11-09 23:58 -- John Hawks

    Ann Gibbons reports [1] from the International Congress of Human Genetics, on papers that examine GWAS risk alleles for type 2 diabetes: "Diabetes Genes Decline Out of Africa" (paywall).

    At the poster session, Stanford graduate student Erik Corona stood in front of a Google Earth map of the world that he finds surprising. On this map he had plotted the frequency of 12 gene variants known to be associated with type 2 diabetes in 51 populations from Australia to Zaire. It shows “a clear gradient of red to green from west to east, from Africa to Asia,” Corona says (see map). “Something strange is going on with type 2 diabetes.”

    This is of course a challenging problem because risk alleles identified in one population may not replicate in other populations. The most well-known example is ApoE4, strongly associated with Alzheimer's Disease in Europeans, but not in Africans. More generally, looking at a set of risk variants that are identified in one population introduces an ascertainment bias that constrains their likely frequencies in other populations. An allele is more likely to yield a statistically significant association with a trait if the allele is not too rare. If we take many alleles associated with a trait, we're likely to see some gradient across populations due to this bias alone.

    Hidden ascertainment bias is a problem we run up against quite a lot. It may not apply in this case, depending on where the risk alleles were identified, in particular since many risk alleles for type 2 diabetes appear to be linked to recent positive selection (explaining why I got interested).

    References

    1. Gibbons A. Diabetes Genes Decline Out of Africa. Science. 2011;334(6056):583 - 583.
    Tags: 
    type 2 diabetes
    health
    Africa
    population structure
    GWAS

  • Archaic genome snooping from GWAS

    Tue, 2011-10-18 22:08 -- John Hawks

    The 23andMe blog reports on a recent genome-wide association study of type 2 diabetes in South Asian people: "SNPWatch: Genetic Variants Associated with Type 2 Diabetes in South Asians and Europeans". The study was published in August in Nature Genetics, by Kooner and colleagues [1]. As described in the post:

    The authors behind this study carried out one of the largest type 2 diabetes studies to date, scanning the genomes of nearly 19,000 people with the disease and 40,000 without it, all of South Asian descent. Their analysis identified six SNPs linked to this condition. When they combined their results with previously published findings in other ethnicities, they found suggestive evidence that five of the six SNPs were also associated with type 2 diabetes in European populations. Similarly, there was some evidence that the majority of the genetic risk factors in Europeans were also linked to disease in South Asians. Only three genetic factors were not shared at all between the two groups.

    Type 2 diabetes is presently a very interesting topic from an evolutionary viewpoint, and we're beginning to think about it very seriously now. Whenever I see a study like this, I quickly look at the Neandertal and Denisovan genomes to see if any interesting patterns emerge. Sharing GWAS SNP alleles is not necessarily very interesting, because the GWAS risk alleles are mostly not causative themselves; each may be linked to some causative allele that remains to be discovered. The linkage is a function of the evolutionary history of that chromosome region, and many of the key historical events that affect linkage happened within the last 10,000 years. So we really shouldn't expect GWAS alleles to be predictive of phenotypes in Neandertals or Denisovans.

    Still, these alleles are associated with disease in living people, and their genotypes in ancient humans may illuminate cases where the evolutionary history links the population across the gene networks that influence disease. A closer examination of the genealogy around these loci will be more informative, but as a first look I often just genotype the archaic genomes for SNPs in a study. The six SNPs reported here include two cases where the archaic genomes have the derived risk alleles, one of them present in Neandertals but not the Denisova genome. Again, that doesn't tell us anything about the phenotype of the ancient people, but worth a closer look to see if one or both of these is an introgressive allele.

    We have here the GWAS Catalog genotypes for all the archaic genomes. Not much actionable information but there are some interesting phenotypes in there. I'll share some more of those later this week.

    References

    1. Kooner JS, Saleheen D, Sim X, Sehmi J, Zhang W, Frossard P, Been LF, Chia K-S, Dimas AS, Hassanali N, et al. Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nature genetics. 2011;43(10):984-9.
    Tags: 
    Neandertal DNA
    Denisova
    type 2 diabetes
    health
    GWAS
Subscribe to type 2 diabetes

Neandertals

For years, I've worked on their bones. Now I'm working on their genes. Read more about the science studying these ancient people.

Denisova

From a finger bone of an ancient human came the record of a completely unexpected population. My lab is working on the science of the Denisova genome.

Acceleration

The advent of agriculture caused natural selection to speed up greatly in humans. We're uncovering some of the ways that populations have rapidly changed during the last 10,000 years.

Malapa

Just outside Johannesburg, the Malapa site is producing some of the most exciting finds in human evolution. This site is the headquarters of the Malapa Soft Tissue Project.