Recovery of trait heritability from whole genome sequence data
By
Pierrick Wainschtein,
Deepti P Jain,
Loic Yengo,
Zhili Zheng,
TOPMed Anthropometry Working Group, Trans-Omics for Precision Medicine Consortium,
L. Adrienne Cupples,
Aladdin H Shadyab,
Barbara McKnight,
Benjamin M Shoemaker,
Braxton D Mitchell,
Bruce M. Psaty,
Charles Kooperberg,
Dan Roden,
Dawood Darbar,
Donna K. Arnett,
Elizabeth A Regan,
Eric Boerwinkle,
Jerome I. Rotter,
Matthew A Allison,
Merry-Lynn N McDonald,
Mina K. Chung,
Nicholas L. Smith,
Patrick T. Ellinor,
Ramachandran S Vasan,
Rasika A. Mathias,
Stephen S. Rich,
Susan R. Heckbert,
Susan Redline,
Xiuqing Guo,
Y-D Ida Chen,
Ching-Ti Liu,
Mariza de Andrade,
Lisa R. Yanek,
Christine M Albert,
Ryan D. Hernandez,
Stephen T. McGarvey,
Kari E. North,
Leslie A Lange,
Bruce S. Weir,
Cathy C Laurie,
Jian Yang,
Peter M. Visscher
Posted 25 Mar 2019
bioRxiv DOI: 10.1101/588020
(published DOI: 10.1530/ey.16.14.15)
Heritability, the proportion of phenotypic variance explained by genetic factors, can be estimated from pedigree data, but such estimates are uninformative with respect to the underlying genetic architecture. Analyses of data from genome-wide association studies (GWAS) on unrelated individuals have shown that for human traits and disease, approximately one-third to two-thirds of heritability is captured by common SNPs. It is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular if the causal variants are rare, or other reasons such as over-estimation of heritability from pedigree data. Here we show that pedigree heritability for height and body mass index (BMI) appears to be fully recovered from whole-genome sequence (WGS) data on 21,620 unrelated individuals of European ancestry. We assigned 47.1 million genetic variants to groups based upon their minor allele frequencies (MAF) and linkage disequilibrium (LD) with variants nearby, and estimated and partitioned variation accordingly. The estimated heritability was 0.79 (SE 0.09) for height and 0.40 (SE 0.09) for BMI, consistent with pedigree estimates. Low-MAF variants in low LD with neighbouring variants were enriched for heritability, to a greater extent for protein altering variants, consistent with negative selection thereon. Cumulatively variants in the MAF range of 0.0001 to 0.1 explained 0.54 (SE 0.05) and 0.51 (SE 0.11) of heritability for height and BMI, respectively. Our results imply that the still missing heritability of complex traits and disease is accounted for by rare variants, in particular those in regions of low LD.
Download data
- Downloaded 9,914 times
- Download rankings, all-time:
- Site-wide: 258 out of 92,755
- In genetics: 18 out of 4,748
- Year to date:
- Site-wide: 973 out of 92,755
- Since beginning of last month:
- Site-wide: 2,016 out of 92,755
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!