Rare genetic variants explain missing heritability in smoking.

Autor:	Jang SK; Department of Psychology, University of Minnesota, Minneapolis, MN, USA., Evans L; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.; Department of Ecology & Evolution, University of Colorado Boulder, Boulder, CO, USA., Fialkowski A; Department of Psychology, University of Minnesota, Minneapolis, MN, USA., Arnett DK; Dean's Office, University of Kentucky College of Public Health, Lexington, KY, USA., Ashley-Koch AE; Department of Medicine, Duke University School of Medicine, Durham, NC, USA., Barnes KC; Division of Biomedical Informatics & Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Becker DM; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., Blangero J; Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA., Bleecker ER; Department of Medicine, University of Arizona, Tucson, AZ, USA., Boorgula MP; Division of Biomedical Informatics & Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Bowden DW; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA., Brody JA; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., Cade BE; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Jenkins BWC; Jackson Heart Study Graduate Training and Education Center, Jackson State University School of Public Health, Jackson, MS, USA., Carson AP; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA., Chavan S; Division of Biomedical Informatics & Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Cupples LA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Custer B; Vitalant Research Institute, San Francisco, CA, USA., Damrauer SM; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Surgery, Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA., David SP; Department of Family Medicine, Prtizker School of Medicine, University of Chicago, Chicago, IL, USA.; NorthShore University HealthSystem, Evanston, IL, USA., de Andrade M; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Dinardo CL; Fundação Pro Sangue, São Paulo, Brazil., Fingerlin TE; Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Center for Genes Environment and Health, National Jewish Health, Denver, CO, USA., Fornage M; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA., Freedman BI; Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA., Garrett ME; Department of Medicine, Duke University School of Medicine, Durham, NC, USA., Gharib SA; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.; Center for Lung Biology, Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA., Glahn DC; Department of Psychiatry, Boston Children's Hosptial and Harvard Medical School, Boston, MA, USA., Haessler J; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Heckbert SR; Department of Epidemiology, University of Washington, Seattle, WA, USA.; Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA., Hokanson JE; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Hou L; Department of Preventive Medicine, Northwestern University, Chicago, IL, USA., Hwang SJ; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Hyman MC; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Judy R; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Justice AE; Department of Population Health Sciences, Geisinger Health System, Danville, PA, USA., Kaplan RC; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA., Kardia SLR; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Kelly S; Department of Pediatrics, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA., Kim W; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Kooperberg C; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Levy D; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.; Framingham Heart Study, Framingham, MA, USA., Lloyd-Jones DM; Department of Preventive Medicine, Northwestern University, Chicago, IL, USA., Loos RJF; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Manichaikul AW; Center for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, VA, USA., Gladwin MT; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Martin LW; Division of Cardiology, School of Medicine and Health Sciences, Washington, DC, USA., Nouraie M; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Melander O; Department of Clinical Sciences, Lund University, Malmö, Sweden.; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden., Meyers DA; Department of Medicine, University of Arizona, Tucson, AZ, USA., Montgomery CG; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., North KE; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Oelsner EC; Division of General Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY, USA., Palmer ND; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA., Payton M; Department of Epidemiology and Biostatistics, Jackson Heart Study Graduate Training and Education Center, Jackson State University School of Public Health, Jackson, MS, USA., Peljto AL; Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA., Peyser PA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Preuss M; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Psaty BM; Cardiovascular Health Research Unit, Department of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, USA., Qiao D; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Rader DJ; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Rafaels N; Division of Biomedical Informatics & Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Redline S; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Reed RM; University of Maryland School of Medicine, Baltimore, MD, USA., Reiner AP; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Rich SS; Center for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, VA, USA., Rotter JI; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Schwartz DA; Department of Medicine, School of Medicine, University of Colorado Denver, Aurora, CO, USA.; Department of Immunology, School of Medicine, University of Colorado Denver, Aurora, CO, USA., Shadyab AH; Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA, USA., Silverman EK; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Smith NL; Department of Epidemiology, University of Washington, Seattle, WA, USA.; Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA, USA., Smith JG; Wallenberg Laboratory/Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden.; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden., Smith AV; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Smith JA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Tang W; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA., Taylor KD; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Telen MJ; Department of Medicine, Duke University School of Medicine, Durham, NC, USA., Vasan RS; Sections of Preventive Medicine and Epidemiology and Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA., Gordeuk VR; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA., Wang Z; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Wiggins KL; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., Yanek LR; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Yang IV; Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA., Young KA; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Young KL; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Zhang Y; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Liu DJ; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA., Keller MC; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA., Vrieze S; Department of Psychology, University of Minnesota, Minneapolis, MN, USA. vrieze@umn.edu.
Jazyk:	angličtina
Zdroj:	Nature human behaviour [Nat Hum Behav] 2022 Nov; Vol. 6 (11), pp. 1577-1586. Date of Electronic Publication: 2022 Aug 04.
DOI:	10.1038/s41562-022-01408-5
Abstrakt:	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.)
Databáze:	MEDLINE
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