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Rare genetic variants explain missing heritability in smoking.
Tuesday,2022-10-11 21:10 America/Los_Angeles — ecterry
| Title | Rare genetic variants explain missing heritability in smoking. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Jang, S-K, Evans, L, Fialkowski, A, Arnett, DK, Ashley-Koch, AE, Barnes, KC, Becker, DM, Bis, JC, Blangero, J, Bleecker, ER, Boorgula, MPreethi, Bowden, DW, Brody, JA, Cade, BE, Jenkins, BWCampbell, Carson, AP, Chavan, S, Cupples, AL, 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, LWarsinger, 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, J Smith, G, 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 |
| Journal | Nat Hum Behav |
| Date Published | 2022 Aug 04 |
| ISSN | 2397-3374 |
| Abstract | <p>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.</p> |
| DOI | 10.1038/s41562-022-01408-5 |
| Alternate Journal | Nat Hum Behav |
| PubMed ID | 35927319 |
| Grant List | 1R01 HL091357 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01HL104608 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01HL087699 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / HL104608 S1 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01AI132476 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01AI114555 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01HL104608 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01HL087699 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / HL104608 S1 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01AI132476 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01AI114555 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01 HL92301 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01 HL67348 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01 NS058700 / NS / NINDS NIH HHS / United States R01 AR48797 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01 DK071891 / DK / NIDDK NIH HHS / United States R01 AG058921 / AG / NIA NIH HHS / United States K01HL135405 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01HL154284 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / U54MD010724 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01 HL113323 / HL / NHLBI NIH HHS / United States U01 HL089856 / HL / NHLBI NIH HHS / United States U01 HL089897 / HL / NHLBI NIH HHS / United States S10OD028685 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / X01HL134588 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01-HL113326 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01HG010297 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / U01HG007416 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01 HL92301 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01 HL67348 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01 NS058700 / NS / NINDS NIH HHS / United States R01 AR48797 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01 DK071891 / DK / NIDDK NIH HHS / United States R01 AG058921 / AG / NIA NIH HHS / United States X01HL134588 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / HL43680 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / HL113338 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / HL R35135818 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / U01 HL089856 / HL / NHLBI NIH HHS / United States U01 HL089897 / HL / NHLBI NIH HHS / United States 5R01DA037904-05 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / P007183802 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / X01HL134588 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / U01 HL089856 / HL / NHLBI NIH HHS / United States U01 HL089897 / HL / NHLBI NIH HHS / United States R01MH100141 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01DA037904 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / R01MH100141 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) / HL079915 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / R01HL68959 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL70769 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL87681 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HHSN268201100007I / HL / NHLBI NIH HHS / United States HHSN268201100007I / HL / NHLBI NIH HHS / United States R01HL68959 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL79915 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL70769 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL87681 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HHSN268201100007I / HL / NHLBI NIH HHS / United States HL068986 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL085251 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL095080 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL073410 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL054457 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL054464 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL054481 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL119443 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL087660 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HHSN268201700001I / HL / NHLBI NIH HHS / United States HHSN268201700002I / HL / NHLBI NIH HHS / United States HHSN268201700003I / HL / NHLBI NIH HHS / United States HHSN268201700004I / HL / NHLBI NIH HHS / United States HHSN268201700005I / HL / NHLBI NIH HHS / United States R01HL68959 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL79915 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL70769 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL87681 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / NO1-HC-25195 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HHSN268201500001I / HL / NHLBI NIH HHS / United States 75N92019D00031 / HL / NHLBI NIH HHS / United States R01 HL092577-06S1 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / N01-HC-65233 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / N01-HC-65234 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HHSN268201300002I / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / N01-HC-65235 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HHSN268201300003I / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / N01-HC-65236 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL054457 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL054464 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL054481 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HL087660 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / HHSN268201100007I / HL / NHLBI NIH HHS / United States HHSN268200617182C / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / U01 HL054457 / HL / NHLBI NIH HHS / United States U01 HL054464 / HL / NHLBI NIH HHS / United States R01 HL119443 / HL / NHLBI NIH HHS / United States R01 HL085571 / HL / NHLBI NIH HHS / United States R01 HL087660 / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States U01HL080295 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / R01HL087652 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / R01HL105756 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / R01HL103612 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / R01HL120393 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / M01 RR07122 / / WFU | Wake Forest School of Medicine (WFSM) / F32 HL085989 / HL / NHLBI NIH HHS / United States M01 RR07122 / / WFU | Wake Forest School of Medicine (WFSM) / F32 HL085989 / HL / NHLBI NIH HHS / United States P60 AG10484 / / WFU | Claude Pepper Older Americans Independence Center, Wake Forest School of Medicine / P60 AG10484 / / WFU | Claude Pepper Older Americans Independence Center, Wake Forest School of Medicine / HHSN268201800013I / MD / NIMHD NIH HHS / United States HHSN268201800013I / MD / NIMHD NIH HHS / United States HHSN268201800011I / HB / NHLBI NIH HHS / United States HHSN268201800012I / HB / NHLBI NIH HHS / United States HHSN268201800010I / HB / NHLBI NIH HHS / United States HHSN268201800011I / HB / NHLBI NIH HHS / United States HHSN268201800012I / HB / NHLBI NIH HHS / United States HHSN268201800005I / HL / NHLBI NIH HHS / United States HHSN268201800007I / HL / NHLBI NIH HHS / United States HHSN268201800005I / HL / NHLBI NIH HHS / United States HHSN268201800007I / HL / NHLBI NIH HHS / United States HHSN268201800003I / HL / NHLBI NIH HHS / United States HHSN268201800003I / HL / NHLBI NIH HHS / United States HHSN268201800006I / HL / NHLBI NIH HHS / United States HHSN268201800006I / HL / NHLBI NIH HHS / United States HHSN268201800004I / HL / NHLBI NIH HHS / United States HHSN268201800004I / HL / NHLBI NIH HHS / United States 3R01HL055673-18S1 / / University of Washington (UW) / HHSN268201500014C / HL / NHLBI NIH HHS / United States U01HL130114 / / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) / R01AG023629 / / U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) / UL1TR001878 / / U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS) / |
ePub date:
22/08