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Eur J Hum Genet. 2010 Oct;18(10):1148-59. doi: 10.1038/ejhg.2010.60. Epub 2010 May 12.

A powerful score test to detect positive selection in genome-wide scans.

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  • 1Department of Statistics, The Texas A&M University, College Station, TX 77843-3143, USA.

Abstract

One of the surest signatures of recent positive selection is a local elevation of advantageous allele frequency and linkage disequilibrium (LD). We proposed to detect such hitchhiking effects by using extended stretches of homozygosity as a surrogate indicator of recent positive selection. An extended haplotype-based homozygosity score test (EHHST) was developed to detect excess homozygosity. The EHHST conditioned on existing LD and it tested the haplotype version of the Hardy-Weinberg equilibrium. Compared with existing popular tests, which usually lack clear distribution, the EHHST is asymptotically normal, which makes analysis and applications easier. In particular, the EHHST facilitates the computation of an asymptotic P-value instead of an empirical P-value, using simulations. We evaluated by simulation that the EHHST led to appropriate false-positive rates, and it had higher or similar power as the existing popular methods. The method was applied to HapMap Phase II data. We were able to replicate previous findings of strong positive selection in 17 autosome genomic regions out of 20 reported candidates. On the basis of high EHHST values and population differentiations, we identified 15 new candidate regions that could undergo recent selection.

PMID:
20461112
[PubMed - indexed for MEDLINE]
PMCID:
PMC2987455
Free PMC Article

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