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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Worldwide population differentiation at disease-associated SNPs
Sean Myles1, Dan Davison, Jeffrey Barrett
1Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. smm367@cornell.edu
BMC Medical Genomics
|June 6, 2008
Summary
Genetic variants associated with common diseases show varied frequencies across global populations. While not significantly more differentiated than random variants, these risk allele frequency differences may explain differing disease prevalence worldwide.
Area of Science:
- Population genetics
- Human genetics
- Complex disease genetics
Background:
- Genome-wide association studies (GWAS) primarily use European ancestry data.
- Limited understanding of genetic risk factor frequencies in diverse populations.
- Investigating the transferability of disease associations across human populations is crucial.
Purpose of the Study:
- To examine population differentiation at disease-associated single nucleotide polymorphisms (SNPs).
- To assess the transferability of common complex disease risk alleles across diverse populations.
- To understand the role of genetic variation in global disease prevalence.
Main Methods:
- Genotyped 25 disease-associated SNPs in ~1000 individuals from 53 global populations.
- Measured allele frequency differences using Fst.
- Compared Fst values of disease SNPs against 2750 random SNPs.
Main Results:
- Disease-associated SNPs showed similar population differentiation to random SNPs on average.
- Significant variation in risk allele frequencies observed across populations.
- Some risk alleles were absent or fixed in certain populations, impacting disease prevalence.
Conclusions:
- Differences in risk allele frequencies between populations are substantial, potentially explaining varying disease prevalence.
- While not typically driven by strong local positive selection, allele frequency variations are significant.
- Disease risk alleles identified in one population may not be universally applicable.
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