Rare variation facilitates inferences of fine-scale population structure in humans.

Abstract:

:Understanding the genetic structure of human populations has important implications for the design and interpretation of disease mapping studies and reconstructing human evolutionary history. To date, inferences of human population structure have primarily been made with common variants. However, recent large-scale resequencing studies have shown an abundance of rare variation in humans, which may be particularly useful for making inferences of fine-scale population structure. To this end, we used an information theory framework and extensive coalescent simulations to rigorously quantify the informativeness of rare and common variation to detect signatures of fine-scale population structure. We show that rare variation affords unique insights into patterns of recent population structure. Furthermore, to empirically assess our theoretical findings, we analyzed high-coverage exome sequences in 6,515 European and African American individuals. As predicted, rare variants are more informative than common polymorphisms in revealing a distinct cluster of European-American individuals, and subsequent analyses demonstrate that these individuals are likely of Ashkenazi Jewish ancestry. Our results provide new insights into the population structure using rare variation, which will be an important factor to account for in rare variant association studies.

journal_name

Mol Biol Evol

authors

O'Connor TD,Fu W,NHLBI GO Exome Sequencing Project.,ESP Population Genetics and Statistical Analysis Working Group, Emily Turner.,Mychaleckyj JC,Logsdon B,Auer P,Carlson CS,Leal SM,Smith JD,Rieder MJ,Bamshad MJ,Nickerson DA,Ake

doi

10.1093/molbev/msu326

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

653-60

issue

3

eissn

0737-4038

issn

1537-1719

pii

msu326

journal_volume

32

pub_type

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