Rare genetic variants explain missing heritability in smoking.

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  • Additional Information
    • Source:
      Publisher: Springer Nature Publishing Country of Publication: England NLM ID: 101697750 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2397-3374 (Electronic) Linking ISSN: 23973374 NLM ISO Abbreviation: Nat Hum Behav Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Springer Nature Publishing, [2017]-
    • Subject Terms:
      Genome-Wide Association Study* ; Polymorphism, Single Nucleotide*/genetics; Gene Frequency ; Phenotype ; Smoking/genetics
    • 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.
      (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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    • Grant Information:
      HHSN268201800003I United States HL NHLBI NIH HHS; HHSN268201800005I United States HL NHLBI NIH HHS; HHSN268201800007I United States HL NHLBI NIH HHS; R01 HL119443 United States HL NHLBI NIH HHS; IK2 CX001780 United States CX CSRD VA; HHSN268201700001I United States HL NHLBI NIH HHS; R01 DA037904 United States DA NIDA NIH HHS; R01 HG011035 United States HG NHGRI NIH HHS; R01 AG058921 United States AG NIA NIH HHS; HHSN268201500014C United States HL NHLBI NIH HHS; HHSN268201500001I United States HL NHLBI NIH HHS; N01HC85081 United States HL NHLBI NIH HHS; R03 OD032630 United States OD NIH HHS; R01 EB015611 United States EB NIBIB NIH HHS; R01 HL153805 United States HL NHLBI NIH HHS; N01HC55222 United States HL NHLBI NIH HHS; R01 HL113338 United States HL NHLBI NIH HHS; HHSN268201800012I United States HB NHLBI NIH HHS; 75N92019D00031 United States HL NHLBI NIH HHS; N01HC85082 United States HL NHLBI NIH HHS; F32 HL085989 United States HL NHLBI NIH HHS; HHSN268201700005I United States HL NHLBI NIH HHS; R01 HL105756 United States HL NHLBI NIH HHS; R01 HL113323 United States HL NHLBI NIH HHS; HHSN268201700004I United States HL NHLBI NIH HHS; R35 HL135818 United States HL NHLBI NIH HHS; R01 HG008983 United States HG NHGRI NIH HHS; HHSN268201200036C United States HL NHLBI NIH HHS; HHSN268201800011I United States HB NHLBI NIH HHS; U01 HL089856 United States HL NHLBI NIH HHS; HHSN268201700003I United States HL NHLBI NIH HHS; HHSN268201800010I United States HB NHLBI NIH HHS; HHSN268200800007C United States HL NHLBI NIH HHS; 75N92021D00006 United States HL NHLBI NIH HHS; U01 HL054457 United States HL NHLBI NIH HHS; R01 DK071891 United States DK NIDDK NIH HHS; R01 HL085571 United States HL NHLBI NIH HHS; R01 MH100141 United States MH NIMH NIH HHS; HHSN268201700002I United States HL NHLBI NIH HHS; N01HC85080 United States HL NHLBI NIH HHS; HHSN268201800006I United States HL NHLBI NIH HHS; R01 NS058700 United States NS NINDS NIH HHS; R01 HL087660 United States HL NHLBI NIH HHS; HHSN268201800001C United States HL NHLBI NIH HHS; HHSN268201800013I United States MD NIMHD NIH HHS; U01 HL089897 United States HL NHLBI NIH HHS; HHSN268201100007I United States HL NHLBI NIH HHS; HHSN268201800004I United States HL NHLBI NIH HHS; R01 DA044283 United States DA NIDA NIH HHS; U01 HL054464 United States HL NHLBI NIH HHS; N01HC85086 United States HL NHLBI NIH HHS; N01HC85079 United States HL NHLBI NIH HHS
    • Publication Date:
      Date Created: 20220804 Date Completed: 20221122 Latest Revision: 20240315
    • Publication Date:
      20240315
    • Accession Number:
      PMC9985486
    • Accession Number:
      10.1038/s41562-022-01408-5
    • Accession Number:
      35927319