Quantifying missing heritability at known GWAS loci.

PLoS Genet
Authors
Keywords
Abstract

Recent work has shown that much of the missing heritability of complex traits can be resolved by estimates of heritability explained by all genotyped SNPs. However, it is currently unknown how much heritability is missing due to poor tagging or additional causal variants at known GWAS loci. Here, we use variance components to quantify the heritability explained by all SNPs at known GWAS loci in nine diseases from WTCCC1 and WTCCC2. After accounting for expectation, we observed all SNPs at known GWAS loci to explain 1.29 x more heritability than GWAS-associated SNPs on average (P=3.3 x 10⁻⁵). For some diseases, this increase was individually significant: 2.07 x for Multiple Sclerosis (MS) (P=6.5 x 10⁻⁹) and 1.48 x for Crohn's Disease (CD) (P = 1.3 x 10⁻³); all analyses of autoimmune diseases excluded the well-studied MHC region. Additionally, we found that GWAS loci from other related traits also explained significant heritability. The union of all autoimmune disease loci explained 7.15 x more MS heritability than known MS SNPs (P 20,000 Rheumatoid Arthritis (RA) samples typed on ImmunoChip, with 2.37 x more heritability from all SNPs at GWAS loci (P = 2.3 x 10⁻⁶) and 5.33 x more heritability from all autoimmune disease loci (P

Year of Publication
2013
Journal
PLoS Genet
Volume
9
Issue
12
Pages
e1003993
Date Published
2013
ISSN
1553-7404
URL
DOI
10.1371/journal.pgen.1003993
PubMed ID
24385918
PubMed Central ID
PMC3873246
Links
Grant list
F32 GM106584 / GM / NIGMS NIH HHS / United States
U01 HG007033 / HG / NHGRI NIH HHS / United States
F32GM106584 / GM / NIGMS NIH HHS / United States
R03HG006731 / HG / NHGRI NIH HHS / United States
U01 GM092691 / GM / NIGMS NIH HHS / United States
R03 HG006731 / HG / NHGRI NIH HHS / United States
R01 AR063759 / AR / NIAMS NIH HHS / United States
R21 ES020754 / ES / NIEHS NIH HHS / United States
20385 / Arthritis Research UK / United Kingdom