학술논문
Rare genetic variants explain missing heritability in smoking.
Document Type
article
Author
Jang, Seon-Kyeong; Evans, Luke; Fialkowski, Allison; Arnett, Donna K; Ashley-Koch, Allison E; Barnes, Kathleen C; Becker, Diane M; Bis, Joshua C; Blangero, John; Bleecker, Eugene R; Boorgula, Meher Preethi; Bowden, Donald W; Brody, Jennifer A; Cade, Brian E; Jenkins, Brenda W Campbell; Carson, April P; Chavan, Sameer; Cupples, L Adrienne; Custer, Brian; Damrauer, Scott M; David, Sean P; de Andrade, Mariza; Dinardo, Carla L; Fingerlin, Tasha E; Fornage, Myriam; Freedman, Barry I; Garrett, Melanie E; Gharib, Sina A; Glahn, David C; Haessler, Jeffrey; Heckbert, Susan R; Hokanson, John E; Hou, Lifang; Hwang, Shih-Jen; Hyman, Matthew C; Judy, Renae; Justice, Anne E; Kaplan, Robert C; Kardia, Sharon LR; Kelly, Shannon; Kim, Wonji; Kooperberg, Charles; Levy, Daniel; Lloyd-Jones, Donald M; Loos, Ruth JF; Manichaikul, Ani W; Gladwin, Mark T; Martin, Lisa Warsinger; Nouraie, Mehdi; Melander, Olle; Meyers, Deborah A; Montgomery, Courtney G; North, Kari E; Oelsner, Elizabeth C; Palmer, Nicholette D; Payton, Marinelle; Peljto, Anna L; Peyser, Patricia A; Preuss, Michael; Psaty, Bruce M; Qiao, Dandi; Rader, Daniel J; Rafaels, Nicholas; Redline, Susan; Reed, Robert M; Reiner, Alexander P; Rich, Stephen S; Rotter, Jerome I; Schwartz, David A; Shadyab, Aladdin H; Silverman, Edwin K; Smith, Nicholas L; Smith, J Gustav; Smith, Albert V; Smith, Jennifer A; Tang, Weihong; Taylor, Kent D; Telen, Marilyn J; Vasan, Ramachandran S; Gordeuk, Victor R; Wang, Zhe; Wiggins, Kerri L; Yanek, Lisa R; Yang, Ivana V; Young, Kendra A; Young, Kristin L; Zhang, Yingze; Liu, Dajiang J; Keller, Matthew C; Vrieze, Scott
Source
Nature human behaviour. 6(11)
Subject
Language
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.