Leveraging population admixture to characterize the heritability of complex traits.

Nat Genet
Authors
Keywords
Abstract

Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2).

Year of Publication
2014
Journal
Nat Genet
Volume
46
Issue
12
Pages
1356-62
Date Published
2014 Dec
ISSN
1546-1718
URL
DOI
10.1038/ng.3139
PubMed ID
25383972
PubMed Central ID
PMC4244251
Links
Grant list
HHSN268201100001I / HL / NHLBI NIH HHS / United States
F32 GM106584 / GM / NIGMS NIH HHS / United States
1K25HL121295-01A1 / HL / NHLBI NIH HHS / United States
U10 CA037429 / CA / NCI NIH HHS / United States
R01 GM100233 / GM / NIGMS NIH HHS / United States
HHSN271201100004C / PHS HHS / United States
P30 CA015704 / CA / NCI NIH HHS / United States
HHSN268201100001C / PHS HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
UG1 CA189974 / CA / NCI NIH HHS / United States
R01 CA092447 / CA / NCI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
R01 HG006399 / HG / NHGRI NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
R01 GM073059 / GM / NIGMS NIH HHS / United States
HHSN268201100003C / PHS HHS / United States
HHSN268201100004C / PHS HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
R21 HL123677 / HL / NHLBI NIH HHS / United States
HHSN268201100046C / PHS HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
R01 ES011126 / ES / NIEHS NIH HHS / United States
HHSN268201100002C / PHS HHS / United States
K25 HL121295 / HL / NHLBI NIH HHS / United States
R21 ES020754 / ES / NIEHS NIH HHS / United States
UM1 CA182883 / CA / NCI NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States