Rare genetic variants explain missing heritability in smoking

Authors

Seon-Kyeong Jang
Luke Evans
Allison Fialkowski
Donna K. Arnett
Allison E. Ashley-Koch
Kathleen C. Barnes
Diane M. Becker
Joshua C. Bis
John Blangero, The University of Texas Rio Grande Valley
Eugene R. Bleecker

Document Type

Article

Publication Date

8-4-2022

Abstract

Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this ‘missing heritability’. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability (h2SNP) was estimated from 0.13 to 0.28 (s.e., 0.10–0.13) in European ancestries, with 35–74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5–4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability (h2ped, 0.18–0.34). In the African ancestry samples, h2SNP was estimated from 0.03 to 0.33 (s.e., 0.09–0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.

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Recommended Citation

Jang, SK., Evans, L., Fialkowski, A. et al. Rare genetic variants explain missing heritability in smoking. Nat Hum Behav (2022). https://doi.org/10.1038/s41562-022-01408-5

Publication Title

Nature Human Behaviour

DOI

10.1038/s41562-022-01408-5

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics