Evidence map›Paper›PMID 35927319›Full record

ArticleNature human behaviour2022

Rare genetic variants explain missing heritability in smoking.

Seon-Kyeong Jang, Luke Evans, Allison Fialkowski, Donna K Arnett, Allison E Ashley-Koch, Kathleen C Barnes, Diane M Becker, Joshua C Bis, John Blangero, Eugene R Bleecker and 80 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature human behaviour, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

90 authors.

Seon-Kyeong JangDepartment of Psychology, University of Minnesota, Minneapolis, MN, USA.
Luke EvansInstitute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.ORCID 0000-0002-7458-1720
Allison FialkowskiDepartment of Psychology, University of Minnesota, Minneapolis, MN, USA.
Donna K ArnettDean's Office, University of Kentucky College of Public Health, Lexington, KY, USA.ORCID 0000-0003-2219-657X
Allison E Ashley-KochDepartment of Medicine, Duke University School of Medicine, Durham, NC, USA.ORCID 0000-0001-5409-9155
Kathleen C BarnesDivision of Biomedical Informatics & Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Diane M BeckerDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0002-3409-1110
John BlangeroDepartment of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
Eugene R BleeckerDepartment of Medicine, University of Arizona, Tucson, AZ, USA.
Meher Preethi BoorgulaDivision of Biomedical Informatics & Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Donald W BowdenDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Brian E CadeDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-1424-0673
Brenda W Campbell JenkinsJackson Heart Study Graduate Training and Education Center, Jackson State University School of Public Health, Jackson, MS, USA.
April P CarsonDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.ORCID 0000-0002-7970-6756
Sameer ChavanDivision of Biomedical Informatics & Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
L Adrienne CupplesDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Brian CusterVitalant Research Institute, San Francisco, CA, USA.ORCID 0000-0001-6251-366X
Scott M DamrauerDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sean P DavidDepartment of Family Medicine, Prtizker School of Medicine, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-4922-2603
Mariza de AndradeDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Carla L DinardoFundação Pro Sangue, São Paulo, Brazil.
Tasha E FingerlinColorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Myriam FornageBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Barry I FreedmanSection on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.ORCID 0000-0003-0275-5530
Melanie E GarrettDepartment of Medicine, Duke University School of Medicine, Durham, NC, USA.ORCID 0000-0003-2302-6150
Sina A GharibCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0002-2480-4367
David C GlahnDepartment of Psychiatry, Boston Children's Hosptial and Harvard Medical School, Boston, MA, USA.
Jeffrey HaesslerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Susan R HeckbertDepartment of Epidemiology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-7100-512X
John E HokansonDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Lifang HouDepartment of Preventive Medicine, Northwestern University, Chicago, IL, USA.
Shih-Jen HwangPopulation Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Matthew C HymanDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-4050-6925
Renae JudyDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Anne E JusticeDepartment of Population Health Sciences, Geisinger Health System, Danville, PA, USA.ORCID 0000-0002-8903-8712
Robert C KaplanDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Shannon KellyDepartment of Pediatrics, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
Wonji KimChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1249-797X
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Daniel LevyPopulation Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Donald M Lloyd-JonesDepartment of Preventive Medicine, Northwestern University, Chicago, IL, USA.
Ruth J F LoosCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-8532-5087
Ani W ManichaikulCenter for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, VA, USA.ORCID 0000-0002-5998-795X
Mark T GladwinDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Lisa Warsinger MartinDivision of Cardiology, School of Medicine and Health Sciences, Washington, DC, USA.ORCID 0000-0003-4352-0914
Mehdi NouraieDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0001-7465-0581
Olle MelanderDepartment of Clinical Sciences, Lund University, Malmö, Sweden.
Deborah A MeyersDepartment of Medicine, University of Arizona, Tucson, AZ, USA.
Courtney G MontgomeryGenes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Kari E NorthDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Elizabeth C OelsnerDivision of General Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY, USA.ORCID 0000-0002-7481-9671
Nicholette D PalmerDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.ORCID 0000-0001-8883-2511
Marinelle PaytonDepartment of Epidemiology and Biostatistics, Jackson Heart Study Graduate Training and Education Center, Jackson State University School of Public Health, Jackson, MS, USA.
Anna L PeljtoDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.ORCID 0000-0002-8389-0736
Patricia A PeyserDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Michael PreussCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-5266-8465
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, USA.ORCID 0000-0002-7278-2190
Dandi QiaoChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-9450-205X
Daniel J RaderDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-9245-9876
Nicholas RafaelsDivision of Biomedical Informatics & Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Susan RedlineDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-6585-1610
Robert M ReedUniversity of Maryland School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-4681-7070
Alexander P ReinerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID 0000-0002-1427-4470
Stephen S RichCenter for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, VA, USA.ORCID 0000-0003-3872-7793
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
David A SchwartzDepartment of Medicine, School of Medicine, University of Colorado Denver, Aurora, CO, USA.ORCID 0000-0001-6743-8443
Aladdin H ShadyabHerbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA, USA.
Edwin K SilvermanChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nicholas L SmithDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
J Gustav SmithWallenberg Laboratory/Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden.ORCID 0000-0001-6285-9935
Albert V SmithDepartment of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3575-5468
Weihong TangDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Kent D TaylorInstitute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Marilyn J TelenDepartment of Medicine, Duke University School of Medicine, Durham, NC, USA.
Ramachandran S VasanSections of Preventive Medicine and Epidemiology and Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.ORCID 0000-0001-7357-5970
Victor R GordeukDepartment of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Zhe WangCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-8046-4969
Kerri L WigginsCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0003-2749-1279
Lisa R YanekDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-7117-1075
Ivana V YangDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Kendra A YoungDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID 0000-0002-8664-7635
Kristin L YoungDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0003-0070-6145
Yingze ZhangDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0001-6947-2901
Dajiang J LiuDepartment of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.ORCID 0000-0001-6553-858X
Matthew C KellerInstitute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Scott VriezeDepartment of Psychology, University of Minnesota, Minneapolis, MN, USA. vrieze@umn.edu.ORCID 0000-0003-3861-7930

Funding

Genetic Epidemiology of COPDU01HL089897 · NHLBI · NATIONAL JEWISH HEALTH · PI CRAPO, JAMES D · 2007 to 2021
$56.9M
FRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · 2019 to 2024
$29.8M
Genetic Epidemiology of COPDU01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2007 to 2021
$20.7M
Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
CARDIOVASCULAR HEALTH STUDY (CHS) - TASK AREA C, STUDY CLOSEOUT75N92021D00006 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE · 2021 to 2024
$8.4M
Whole Genome Sequencing to Identify Causal Genetic Variants Influencing CVD RiskR01HL113323 · NHLBI · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · PI BLANGERO, JOHN, CURRAN, JOANNE E. · 2012 to 2016
$8.2M
Phenotypic and Molecular Signatures for Sleep Apnea and Related MorbiditiesR35HL135818 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI REDLINE, SUSAN S. · 2017 to 2023
$7.2M
Rare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6M
Estimating the genetic and environmental architecture of psychiatric disordersR01MH100141 · NIMH · UNIVERSITY OF COLORADO · PI KELLER, MATTHEW CHARLES · 2013 to 2022
$5.3M
Genomic Predictors of Arteriosclerosis in HypertensivesR01HL087660 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KARDIA, SHARON L · 2007 to 2009
$5.1M
CSRD VA IK2 CX001780NHGRI NIH HHS R01 HG008983NHGRI NIH HHS R01 HG011035NHLBI NIH HHS 75N92019D00031NHLBI NIH HHS 75N92021D00006NHLBI NIH HHS F32 HL085989NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS HHSN268201500014CNHLBI NIH HHS HHSN268201700001INHLBI NIH HHS HHSN268201700002INHLBI NIH HHS HHSN268201700003INHLBI NIH HHS HHSN268201700004INHLBI NIH HHS HHSN268201700005INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS HHSN268201800003INHLBI NIH HHS HHSN268201800004INHLBI NIH HHS HHSN268201800005INHLBI NIH HHS HHSN268201800006INHLBI NIH HHS HHSN268201800007INHLBI NIH HHS HHSN268201800010INHLBI NIH HHS HHSN268201800011INHLBI NIH HHS HHSN268201800012INHLBI NIH HHS N01HC55222NHLBI NIH HHS N01HC85079NHLBI NIH HHS N01HC85080NHLBI NIH HHS N01HC85081NHLBI NIH HHS N01HC85082NHLBI NIH HHS N01HC85086NHLBI NIH HHS R01 HL085571NHLBI NIH HHS R01 HL087660NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL113323NHLBI NIH HHS R01 HL113338NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL119443NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL153805NHLBI NIH HHS R35 HL135818NHLBI NIH HHS U01 HL054457NHLBI NIH HHS U01 HL054464NHLBI NIH HHS U01 HL089856NHLBI NIH HHS U01 HL089897NHLBI NIH HHS U01 HL120393NIA NIH HHS R01 AG058921NIBIB NIH HHS R01 EB015611NIDA NIH HHS R01 DA037904NIDA NIH HHS R01 DA044283NIDDK NIH HHS R01 DK071891NIH HHS R03 OD032630NIMHD NIH HHS HHSN268201800013INIMH NIH HHS R01 MH100141NINDS NIH HHS R01 NS058700
6 · The paper itself

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.

Indexed as

Genome-Wide Association StudyPolymorphism, Single NucleotideGene FrequencyPhenotypeSmoking

Identifiers

PMID35927319
PMCPMC9985486

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