Rare genetic variants explain missing heritability in smoking.
Journal
Nature human behaviour
ISSN: 2397-3374
Titre abrégé: Nat Hum Behav
Pays: England
ID NLM: 101697750
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
28
04
2021
accepted:
10
06
2022
pubmed:
5
8
2022
medline:
23
11
2022
entrez:
4
8
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35927319
doi: 10.1038/s41562-022-01408-5
pii: 10.1038/s41562-022-01408-5
pmc: PMC9985486
mid: NIHMS1839470
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1577-1586Subventions
Organisme : NHLBI NIH HHS
ID : HHSN268201800003I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800005I
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB015611
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800007I
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG008983
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL119443
Pays : United States
Organisme : CSRD VA
ID : IK2 CX001780
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700001I
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA037904
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG011035
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058921
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500014C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500001I
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85081
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800012I
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL153805
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC55222
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92019D00031
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85082
Pays : United States
Organisme : NHLBI NIH HHS
ID : F32 HL085989
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700005I
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL113323
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700004I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200036C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800011I
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089856
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700003I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800010I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200800007C
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92021D00006
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL054457
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK071891
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL085571
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH100141
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201700002I
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85080
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800006I
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS058700
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL087660
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800001C
Pays : United States
Organisme : NIMHD NIH HHS
ID : HHSN268201800013I
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089897
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100007I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800004I
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA044283
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL054464
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85086
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85079
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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