Rare genetic variants explain missing heritability in smoking

Autor:	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, Eugene R. Bleecker, Meher Preethi Boorgula, Donald W. Bowden, Jennifer A. Brody, Brian E. Cade, Brenda W. Campbell Jenkins, April P. Carson, Sameer Chavan, L. Adrienne Cupples, Brian Custer, Scott M. Damrauer, Sean P. David, Mariza de Andrade, Carla L. Dinardo, Tasha E. Fingerlin, Myriam Fornage, Barry I. Freedman, Melanie E. Garrett, Sina A. Gharib, David C. Glahn, Jeffrey Haessler, Susan R. Heckbert, John E. Hokanson, Lifang Hou, Shih-Jen Hwang, Matthew C. Hyman, Renae Judy, Anne E. Justice, Robert C. Kaplan, Sharon L. R. Kardia, Shannon Kelly, Wonji Kim, Charles Kooperberg, Daniel Levy, Donald M. Lloyd-Jones, Ruth J. F. Loos, Ani W. Manichaikul, Mark T. Gladwin, Lisa Warsinger Martin, Mehdi Nouraie, Olle Melander, Deborah A. Meyers, Courtney G. Montgomery, Kari E. North, Elizabeth C. Oelsner, Nicholette D. Palmer, Marinelle Payton, Anna L. Peljto, Patricia A. Peyser, Michael Preuss, Bruce M. Psaty, Dandi Qiao, Daniel J. Rader, Nicholas Rafaels, Susan Redline, Robert M. Reed, Alexander P. Reiner, Stephen S. Rich, Jerome I. Rotter, David A. Schwartz, Aladdin H. Shadyab, Edwin K. Silverman, Nicholas L. Smith, J. Gustav Smith, Albert V. Smith, Jennifer A. Smith, Weihong Tang, Kent D. Taylor, Marilyn J. Telen, Ramachandran S. Vasan, Victor R. Gordeuk, Zhe Wang, Kerri L. Wiggins, Lisa R. Yanek, Ivana V. Yang, Kendra A. Young, Kristin L. Young, Yingze Zhang, Dajiang J. Liu, Matthew C. Keller, Scott Vrieze
Rok vydání:	2022
Předmět:	Social Psychology Tobacco Smoke and Health Smoking Human Genome Experimental and Cognitive Psychology Single Nucleotide Polymorphism Single Nucleotide Article Behavioral Neuroscience Phenotype Gene Frequency Tobacco Genetics Polymorphism Genome-Wide Association Study Cancer
Zdroj:	Nature human behaviour, vol 6, iss 11 Nat Hum Behav
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::30aa88d7690dcca16453c7af4c2f580f https://escholarship.org/uc/item/3v26257d Zobrazit plný text záznamu