Genome-Wide Association Studies in an Isolated Founder Population from the Pacific Island of Kosrae
2009

Genome-Wide Association Studies in an Isolated Founder Population from the Pacific Island of Kosrae

Sample size: 2906 publication Evidence: moderate

Author Information

Author(s): Lowe Jennifer K., Maller Julian B., Pe'er Itsik, Neale Benjamin M., Salit Jacqueline, Kenny Eimear E., Shea Jessica L., Burkhardt Ralph, Smith J. Gustav, Ji Weizhen, Noel Martha, Foo Jia Nee, Blundell Maude L., Skilling Vita, Garcia Laura, Sullivan Marcia L., Lee Heather E., Labek Anna, Ferdowsian Hope, Auerbach Steven B., Lifton Richard P., Newton-Cheh Christopher, Breslow Jan L., Stoffel Markus, Daly Mark J., Altshuler David M., Friedman Jeffrey M.

Primary Institution: The Rockefeller University

Hypothesis

We hypothesized that genetic drift and possibly natural selection on Kosrae might have increased the frequency of previously rare genetic variants with relatively large effects.

Conclusion

The study found that even in a severely inbred population, common alleles typically have modest effects on complex traits.

Supporting Evidence

  • The study observed associations to known loci for plasma cholesterol, triglycerides, and C-reactive protein.
  • Common alleles explaining ≥5% phenotypic variance were detectable, but no large effects were observed with genome-wide significance.
  • Many common variants discovered in Caucasians had indistinguishable effect sizes on Kosrae.

Takeaway

Scientists studied people from Kosrae to see if they could find strong genetic links to health problems, but they mostly found that common genes have small effects.

Methodology

Genome-wide association analysis for 15 quantitative traits was performed in 2,906 members of the Kosrae population using novel approaches to manage relatedness.

Potential Biases

The extensive relatedness between subjects may violate the assumptions of independence in traditional association tests.

Limitations

The study's power is limited due to the small sample size and the relatedness among participants.

Participant Demographics

The study included 2,906 individuals from the Kosrae population, with a gender distribution of approximately 41.6% male and 58.4% female.

Statistical Information

P-Value

p<5×10−8

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pgen.1000365

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