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Rare genetic variants explain missing heritability in smoking.

Publication ,  Journal Article
Jang, S-K; Evans, L; Fialkowski, A; Arnett, DK; Ashley-Koch, AE; Barnes, KC; Becker, DM; Bis, JC; Blangero, J; Bleecker, ER; Boorgula, MP ...
Published in: Nat Hum Behav
November 2022

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.

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Published In

Nat Hum Behav

DOI

EISSN

2397-3374

Publication Date

November 2022

Volume

6

Issue

11

Start / End Page

1577 / 1586

Location

England

Related Subject Headings

  • Smoking
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Genome-Wide Association Study
  • Gene Frequency
  • 52 Psychology
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
 

Citation

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Jang, S.-K., Evans, L., Fialkowski, A., Arnett, D. K., Ashley-Koch, A. E., Barnes, K. C., … Vrieze, S. (2022). Rare genetic variants explain missing heritability in smoking. Nat Hum Behav, 6(11), 1577–1586. https://doi.org/10.1038/s41562-022-01408-5
Jang, Seon-Kyeong, Luke Evans, Allison Fialkowski, Donna K. Arnett, Allison E. Ashley-Koch, Kathleen C. Barnes, Diane M. Becker, et al. “Rare genetic variants explain missing heritability in smoking.Nat Hum Behav 6, no. 11 (November 2022): 1577–86. https://doi.org/10.1038/s41562-022-01408-5.
Jang S-K, Evans L, Fialkowski A, Arnett DK, Ashley-Koch AE, Barnes KC, et al. Rare genetic variants explain missing heritability in smoking. Nat Hum Behav. 2022 Nov;6(11):1577–86.
Jang, Seon-Kyeong, et al. “Rare genetic variants explain missing heritability in smoking.Nat Hum Behav, vol. 6, no. 11, Nov. 2022, pp. 1577–86. Pubmed, doi:10.1038/s41562-022-01408-5.
Jang S-K, Evans L, Fialkowski A, Arnett DK, Ashley-Koch AE, Barnes KC, Becker DM, Bis JC, Blangero J, Bleecker ER, Boorgula MP, Bowden DW, Brody JA, Cade BE, Jenkins BWC, Carson AP, Chavan S, Cupples LA, Custer B, Damrauer SM, David SP, de Andrade M, Dinardo CL, Fingerlin TE, Fornage M, Freedman BI, Garrett ME, Gharib SA, Glahn DC, Haessler J, Heckbert SR, Hokanson JE, Hou L, Hwang S-J, Hyman MC, Judy R, Justice AE, Kaplan RC, Kardia SLR, Kelly S, Kim W, Kooperberg C, Levy D, Lloyd-Jones DM, Loos RJF, Manichaikul AW, Gladwin MT, Martin LW, Nouraie M, Melander O, Meyers DA, Montgomery CG, North KE, Oelsner EC, Palmer ND, Payton M, Peljto AL, Peyser PA, Preuss M, Psaty BM, Qiao D, Rader DJ, Rafaels N, Redline S, Reed RM, Reiner AP, Rich SS, Rotter JI, Schwartz DA, Shadyab AH, Silverman EK, Smith NL, Smith JG, Smith AV, Smith JA, Tang W, Taylor KD, Telen MJ, Vasan RS, Gordeuk VR, Wang Z, Wiggins KL, Yanek LR, Yang IV, Young KA, Young KL, Zhang Y, Liu DJ, Keller MC, Vrieze S. Rare genetic variants explain missing heritability in smoking. Nat Hum Behav. 2022 Nov;6(11):1577–1586.

Published In

Nat Hum Behav

DOI

EISSN

2397-3374

Publication Date

November 2022

Volume

6

Issue

11

Start / End Page

1577 / 1586

Location

England

Related Subject Headings

  • Smoking
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Genome-Wide Association Study
  • Gene Frequency
  • 52 Psychology
  • 42 Health sciences
  • 32 Biomedical and clinical sciences