Faculty, Staff and Student Publications
Publication Date
11-1-2022
Journal
Nature Human Behaviour
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 ([Formula: see text]) 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 ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] 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.
Keywords
Genome-Wide Association Study, Gene Frequency, Polymorphism, Single Nucleotide, Phenotype, Smoking
DOI
10.1038/s41562-022-01408-5
PMID
35927319
PMCID
PMC9985486
PubMedCentral® Posted Date
5-1-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Included in
Behavioral Medicine Commons, Public Health Commons, Substance Abuse and Addiction Commons