Signals of polygenic adaptation on height have been overestimated due to uncorrected population structure in genome-wide association studies
By M. Sohail, Robert M. Maier, A. Ganna, Alex Bloemendal, Alicia R. Martin, M. Turchin, C. Chiang, Joel Hirschhorn, Mark J. Daly, Nick Patterson and 4 more. 2018
30 citations recorded by the source corpus.
Genetic predictions of height differ among human populations and these differences are too large to be explained by genetic drift. This observation has been interpreted as evidence of polygenic adaptation. Differences across populations were detected using SNPs genome-wide significantly associated with height, and many studies also found that the signals grew stronger when large numbers of subsignificant SNPs were analyzed. This has led to excitement about the prospect of analyzing large fractions of the genome to detect subtle signals of selection and claims of polygenic adaptation for multiple traits. Polygenic adaptation studies of height have been based on SNP effect size measurements in the GIANT Consortium meta-analysis. Here we repeat the height analyses in the UK Biobank, a much more homogeneously designed study. Our results show that polygenic adaptation signals based on large numbers of SNPs below genome-wide significance are extremely sensitive to biases due to uncorrected population structure.
Subfields: Genetics
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In Genetics
- Graham Coop
- Mark J. Daly
- J. K. Pritchard
- Alicia R. Martin
- Matti Pirinen
- Evan A. Boyle
- A. Harpak
- Fernando Racimo
Citations in the corpus
- Geographic variation and bias in polygenic scores of complex diseases and traits in Finland (2018, background): “A few possible reasons for this bias accumulation could be inadequate adjustment for population structure in GWAS (Sohail et al. 2018, Berg et al. 2018) or partially overlapping or related samples between GWAS samples and test data.”
- Reduced signal for polygenic adaptation of height in UK Biobank (2018, result): “Similar findings have been obtained independently by other groups [21, 22].”