ArticleGenetics2021
Robust, flexible, and scalable tests for Hardy-Weinberg equilibrium across diverse ancestries.
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Article in Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14citing papers in PubMed
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Who cites it
14 citing papers in PubMed.
- Assessing Hardy-Weinberg equilibrium in T2T-aligned 1000 genomes project.PLoS genetics · 2026Article
- Whole genome sequencing analysis of over 3500 individuals dementia-free over 85 years old.Journal of Alzheimer's disease : JAD · 2026Article
- Application of the STAAR framework in detecting rare variant associations with Alzheimer disease and related dementias: Insights and implications.HGG advances · 2026Article
- Hardy-Weinberg Equilibrium Filtering in Population Genomics: Empirical Review and Decision Framework for Improved Practice.Ecology and evolution · 2026Review
- Circulating Proteomic Profiles Are Associated With Incident Type 2 Diabetes in Asian Populations.The Journal of clinical endocrinology and metabolism · 2025Article
- Nuclear regulatory disturbances precede and predict the development of Type-2 diabetes in Asian populations.medRxiv : the preprint server for health sciences · 2025Article
- Gene-based Hardy-Weinberg equilibrium test using genotype count data: application to six types of cancers.BMC genomics · 2025Article
- Association of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole-genome sequencing from the Alzheimer's Disease Sequencing Project.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Semi-supervised machine learning method for predicting homogeneous ancestry groups to assess Hardy-Weinberg equilibrium in diverse whole-genome sequencing studies.American journal of human genetics · 2024Article
- Integrated clinical risk prediction of type 2 diabetes with a multifactorial polygenic risk score.medRxiv : the preprint server for health sciences · 2024Article
- Efficient test for deviation from Hardy-Weinberg equilibrium with known or ambiguous typing in highly polymorphic loci.Briefings in bioinformatics · 2024Article
- Hardy-Weinberg Equilibrium in Meta-Analysis Studies and Large-Scale Genomic Sequencing Era.Asian Pacific journal of cancer prevention : APJCP · 2024Review
- eXclusionarY: 10 years later, where are the sex chromosomes in GWASs?American journal of human genetics · 2023Review
- FixItFelix: improving genomic analysis by fixing reference errors.Genome biology · 2023Article
Corrections and comments
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Authors and funding
48 authors.
Alan M KwongDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Thomas W BlackwellDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Jonathon LeFaiveDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Mariza de AndradeMayo Clinic, Rochester, MN 55905, USA.
John BarnardDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Kathleen C BarnesDepartment of Medicine, Anschultz Medical Campus, University of Colorado, Aurora, CO 80045, USA.
John BlangeroDepartment of Human Genetics, South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA.
Eric BoerwinkleDepartment of Epidemiology, Human Genetics Center, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Esteban G BurchardDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94143, USA.
Brian E CadeDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115, USA.
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
Han ChenDepartment of Epidemiology, Human Genetics Center, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Matthew P ConomosDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
L Adrienne CupplesDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Patrick T EllinorCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Celeste EngDepartment of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Yan GaoDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216 USA.
Xiuqing GuoDepartment of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Marguerite Ryan IrvinDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Tanika N KellyDepartment of Epidemiology, Tulane University, New Orleans, LA 70112, USA.
Wonji KimChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Charles KooperbergFred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Steven A LubitzCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Angel C Y MakDepartment of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Ani W ManichaikulDepartment of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
Rasika A MathiasGeneSTAR Research Program and Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
May E MontasserDivision of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Courtney G MontgomerySarcoidosis Research Unit, Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Solomon MusaniJackson Heart Study, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Nicholette D PalmerDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Gina M PelosoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Dandi QiaoChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Alexander P ReinerFred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Dan M RodenDepartments of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
M Benjamin ShoemakerDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
Nicholas L SmithDepartment of Epidemiology, University of Washington, Seattle, WA 98195, USA.
Jessica Lasky SuChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Hemant K TiwariDepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Daniel E WeeksDepartments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Scott T WeissChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
TOPMed Analysis Working Group
Laura J ScottDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Albert V SmithDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Gonçalo R AbecasisDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Michael BoehnkeDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Hyun Min KangDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Funding
Tracking and Evaluation CoreU54GM104938 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Janis E Campbell · 2013 to 2026
$68.2MPEDIGREE ANALYSIS OF LIPOPROTEIN PHENOTYPESP01HL045522 · NHLBI · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI BLANGERO, JOHN · 1991 to 2012
$27.6MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3MSystems Biology of Airway DiseaseP01HL132825 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DEMEO, DAWN L · 2016 to 2020
$12.6MStudies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5MRare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9MComprehensive Genome Interrogation of African American Sarcoidosis FamiliesR01HL113326 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI MONTGOMERY, COURTNEY · 2012 to 2022
$8.7MStudies of Rare Genetic Variation in the Isolated Population of SardiniaU01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2017 to 2018
$6.3MRare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6MWhole genome sequences in individuals to comprehensively characterize the genetic mechanisms of dyslipidemiasR01HL142711 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Satoshi Koyama, Gina Marie Peloso · 2019 to 2026
$4.7MWomen's Health Study: Infrastructure support for continued cohort follow-upU01CA182913 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 2019 to 2023
$4.0MMulti-omic studies of asthma severity in an African ancestry populationR01AI132476 · NIAID · UNIVERSITY OF COLORADO DENVER · PI BARNES, KATHLEEN C, MATHIAS, RASIKA ANN · 2018 to 2022
$3.5MNCI NIH HHS U01 CA182913NHGRI NIH HHS R01 HG007022NHGRI NIH HHS R01 HG009976NHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS K01 HL129039NHLBI NIH HHS K01 HL135405NHLBI NIH HHS P01 HL045522NHLBI NIH HHS P01 HL132825NHLBI NIH HHS R01 HL113326NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL142711NHLBI NIH HHS R03 HL154284NHLBI NIH HHS U01 HL117626NHLBI NIH HHS U01 HL120393NHLBI NIH HHS U01 HL137182NIAID NIH HHS R01 AI132476NIDA NIH HHS R01 DA037904NIDDK NIH HHS P30 DK020572NIGMS NIH HHS U54 GM104938NIMH NIH HHS U01 MH105653
Abstract
Traditional Hardy-Weinberg equilibrium (HWE) tests (the χ2 test and the exact test) have long been used as a metric for evaluating genotype quality, as technical artifacts leading to incorrect genotype calls often can be identified as deviations from HWE. However, in data sets composed of individuals from diverse ancestries, HWE can be violated even without genotyping error, complicating the use of HWE testing to assess genotype data quality. In this manuscript, we present the Robust Unified Test for HWE (RUTH) to test for HWE while accounting for population structure and genotype uncertainty, and to evaluate the impact of population heterogeneity and genotype uncertainty on the standard HWE tests and alternative methods using simulated and real sequence data sets. Our results demonstrate that ignoring population structure or genotype uncertainty in HWE tests can inflate false-positive rates by many orders of magnitude. Our evaluations demonstrate different tradeoffs between false positives and statistical power across the methods, with RUTH consistently among the best across all evaluations. RUTH is implemented as a practical and scalable software tool to rapidly perform HWE tests across millions of markers and hundreds of thousands of individuals while supporting standard VCF/BCF formats. RUTH is publicly available at https://www.github.com/statgen/ruth.
Indexed as
AllelesGene FrequencyGenetics, PopulationGenotypeHumansLinkage DisequilibriumModels, GeneticModels, StatisticalPhenotypeSoftwaregenotype likelihoodsnext-generation sequencingpopulation structureprincipal components analysis
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.