ArticleNature communications2021
Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 2 pooled it
13.0field-weighted citation impact, top 1% of its field
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.
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.
Who cites it
67 citing papers in PubMed, 2 syntheses or guidelines pooled it, 105 citations in OpenAlex.
- Pooled it
- Rare variant analyses in 51,256 type 2 diabetes cases and 370,487 controls reveal the pathogenicity spectrum of monogenic diabetes genes.Nature genetics · 2024Pooled it
- Limited penetrance of dominantly inherited AIRE variants in a population-based cohort.Human molecular genetics · 2026Article
- Article
- Sequencing and health data resource of children of African ancestry.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Polygenic backgrounds influence phenotypic consequences of variants in cells, individuals, and populations.Cell genomics · 2026Review
- A new form of diabetes caused by INS mutations defined by zygosity, stem cell and population data.EMBO molecular medicine · 2026Article
- Characterization of monogenic diabetes among Sudanese children: a multi-center experience from a population with high consanguinity.Journal of pediatric endocrinology & metabolism : JPEM · 2026Article
- Case Report: NovelFrontiers in medicine · 2026Article
- Interactions with polygenic background impact quantitative traits in the UK Biobank.medRxiv : the preprint server for health sciences · 2025Article
- A scalable approach for genomic-first rare disorder detection in a healthcare-based population.American journal of human genetics · 2025Article
- Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database.Nature communications · 2025Article
- Identification of a NovelGenes · 2025Article
- Management of Type 2 Diabetes Mellitus in Native Americans and Alaska Natives: A Systematic Review.Journal of racial and ethnic health disparities · 2025Review
- SPINK1-related chronic pancreatitis: A model that encapsulates the spectrum of variant effects, genetic complexity, and classificatory challenges.American journal of human genetics · 2025Article
- The Causal Pivot: A structural approach to genetic heterogeneity and variant discovery in complex diseases.American journal of human genetics · 2025Article
- Influence of Polygenic Risk on Height and BMI in Adults With a 22q11.2 Microdeletion.Journal of the Endocrine Society · 2025Article
- Diabetes mellitus polygenic risk scores: heterogeneity and clinical translation.Nature reviews. Endocrinology · 2025Review
- A gain-of-function mutation in ATP6V0A4 drives primary distal renal tubular alkalosis with enhanced V-ATPase activity.The Journal of clinical investigation · 2025Article
- Investigating the sources of variable impact of pathogenic variants in monogenic metabolic conditions.Nature communications · 2025Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
131 authors at 20 institutions in 21 countries.
Julia K GoodrichProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Moriel Singer-BerkProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Rachel SonProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Abigail SvedenProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jordan WoodProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Eleina EnglandProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Joanne B ColeProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-9520-2788
Ben WeisburdProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nick WattsProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Lizz CaulkinsProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Peter DornbosProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ryan KoestererProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Zachary ZappalaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-6289-1481
Haichen ZhangSchool of Medicine, University of Maryland Baltimore, Baltimore, MD, USA.ORCID 0000-0002-0615-2836
Kristin A MaloneySchool of Medicine, University of Maryland Baltimore, Baltimore, MD, USA.ORCID 0000-0002-8607-1146
Andy DahlDepartment of Neurology, UCLA, Los Angeles, CA, USA.ORCID 0000-0001-6520-4766
Carlos A Aguilar-SalinasInstituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico.
Gil AtzmonDepartment of Medicine, Albert Einstein College of Medicine, New York, NY, USA.ORCID 0000-0001-6895-3607
Francisco Barajas-OlmosInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Nir BarzilaiDepartment of Medicine, Albert Einstein College of Medicine, New York, NY, USA.
John BlangeroDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville and Edinburg, TX, USA.ORCID 0000-0001-6250-5723
Eric BoerwinkleHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Lori L BonnycastleMedical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Erwin BottingerThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Donald W BowdenCenter for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Federico Centeno-CruzInstituto Nacional de Medicina Genómica, Mexico City, Mexico.ORCID 0000-0002-3512-4519
John C ChambersDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK.
Nathalie ChamiThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-8547-6424
Edmund ChanDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
Juliana ChanDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
Ching-Yu ChengSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Yoon Shin ChoDepartment of Biomedical Science, Hallym University, Chuncheon, South Korea.
Cecilia Contreras-CubasInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Emilio CórdovaInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Adolfo CorreaDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.ORCID 0000-0002-9501-600X
Ralph A DeFronzoDepartment of Medicine, University of Texas Health San Antonio (aka University of Texas Health Science Center at San Antonio), San Antonio, TX, USA.
Ravindranath DuggiralaDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville and Edinburg, TX, USA.
Josée DupuisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.ORCID 0000-0003-2871-3603
Ma Eugenia Garay-SevillaDepartment of Medical Science, División of Health Science, University of Guanjuato. Campus León. León, Guanjuato, Mexico.
Humberto García-OrtizInstituto Nacional de Medicina Genómica, Mexico City, Mexico.ORCID 0000-0002-0453-980X
Christian GiegerResearch Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Benjamin GlaserEndocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.ORCID 0000-0003-4711-5000
Clicerio González-VillalpandoUnidad de Investigacion en Diabetes y Riesgo Cardiovascular, Instituto Nacional de Salud Publica, Cuernavaca, Mexico.
Ma Elena GonzalezCentro de Estudios en Diabetes, Mexico City, Mexico.
Niels GrarupNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0001-5526-1070
Leif GroopDepartment of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden.ORCID 0000-0002-0187-3263
Myron GrossDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Christopher HaimanDepartment of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA.
Sohee HanDivision of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea.
Craig L HanisHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Torben HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0001-8748-3831
Nancy L Heard-CostaBoston University and National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.ORCID 0000-0001-9730-0306
Brian E HendersonDepartment of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA.
Juan Manuel Malacara HernandezDepartment of Medical Science, División of Health Science, University of Guanjuato. Campus León. León, Guanjuato, Mexico.
Mi Yeong HwangDivision of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea.
Sergio Islas-AndradeInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Marit E JørgensenSteno Diabetes Center Copenhagen, Gentofte, Denmark.
Hyun Min KangDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Bong-Jo KimDivision of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea.
Young Jin KimDivision of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea.ORCID 0000-0002-4132-4437
Heikki A KoistinenDepartment of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland.ORCID 0000-0001-7870-070X
Jaspal Singh KoonerDepartment of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, London, UK.
Johanna KuusistoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Soo-Heon KwakDepartment of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Markku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.ORCID 0000-0002-3394-7749
Leslie LangeDepartment of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
Jong-Young LeeOneomics Soonchunhyang Mirae Medical Center, Bucheon-si Gyeonggi-do, Republic of Korea.ORCID 0000-0002-0092-9958
Juyoung LeeDivision of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea.
Donna M LehmanDepartment of Medicine, University of Texas Health San Antonio (aka University of Texas Health Science Center at San Antonio), San Antonio, TX, USA.
Allan LinnebergDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-0994-0184
Jianjun LiuDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.ORCID 0000-0002-3255-3019
Ruth J F LoosThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-8532-5087
Valeriya LyssenkoCentro de Estudios en Diabetes, Mexico City, Mexico.
Ronald C W MaDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.ORCID 0000-0002-1227-803X
Angélica Martínez-HernándezInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
James B MeigsProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Thomas MeitingerInstitute of Human Genetics, Technical University of Munich, Munich, Germany.
Elvia Mendoza-CaamalInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Karen L MohlkeDepartment of Genetics, University of North Carolina Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-6721-153X
Andrew D MorrisWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Alanna C MorrisonHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Maggie C Y NgCenter for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Peter M NilssonDepartment of Clinical Sciences, Medicine, Lund University, Malmö, Sweden.ORCID 0000-0002-5652-8459
Christopher J O'DonnellDepartment of Pediatrics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-2667-8624
Lorena OrozcoInstituto Nacional de Medicina Genómica, Mexico City, Mexico.ORCID 0000-0002-5801-9180
Colin N A PalmerPat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, University of Dundee, Dundee, UK.ORCID 0000-0002-6415-6560
Kyong Soo ParkDepartment of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.ORCID 0000-0003-3597-342X
Wendy S PostDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Oluf PedersenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-3321-3972
Michael PreussThe Charles 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, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.
Alexander P ReinerFred Hutchinson Cancer Research Center, Seattle, WA, USA.
Cristina Revilla-MonsalveInstituto Nacional de Medicina Genómica, Mexico City, Mexico.ORCID 0000-0002-6202-1160
Stephen S RichCenter for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation (formerly Los Angeles Biomedical Research Institute) at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID 0000-0001-7191-1723
Danish SaleheenDivision of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, PA, USA.
Claudia SchurmannThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-4158-9192
Xueling SimSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.ORCID 0000-0002-1233-7642
Rob SladekDepartment of Human Genetics, McGill University, Montreal, QC, Canada.ORCID 0000-0002-2730-1204
Kerrin S SmallDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID 0000-0003-4566-0005
Wing Yee SoDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
Timothy D SpectorDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID 0000-0002-9795-0365
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany.
Tim M StromInstitute of Human Genetics, Technical University of Munich, Munich, Germany.
E Shyong TaiDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
Claudia H T TamDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.ORCID 0000-0002-9169-0013
Yik Ying TeoSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Farook ThameemDepartment of Biochemistry, Faculty of Medicine, Health Science Center, Kuwait University, Safat, Kuwait.
Brian TomlinsonFaculty of Medicine, Macau University of Science & Technology, Macau, China.ORCID 0000-0001-6717-5444
Russell P TracyDepartment of Pathology and Laboratory Medicine, The Robert Larner M.D. College of Medicine, University of Vermont, Burlington, VT, USA.ORCID 0000-0002-0080-2420
Tiinamaija TuomiDepartment of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden.ORCID 0000-0002-8306-6202
Jaakko TuomilehtoPublic Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.
Teresa Tusié-LunaUnidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Rob M van DamDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
Ramachandran S VasanBoston University and National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.ORCID 0000-0001-7357-5970
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
Daniel R WitteDepartment of Public Health, Aarhus University, Aarhus, Denmark.
Tien-Yin WongSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
AMP-T2D-GENES Consortia
Noël P BurttProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Noah ZaitlenDepartment of Neurology, UCLA, Los Angeles, CA, USA.
Mark I McCarthyOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-6442-7754
Toni I PollinSchool of Medicine, University of Maryland Baltimore, Baltimore, MD, USA.
Jason FlannickProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-3618-795X
Josep M MercaderProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-8494-3660
Anne O'Donnell-LuriaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-6418-9592
Samantha BaxterProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jose C FlorezProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Daniel G MacArthurProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-5771-2290
Miriam S UdlerProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. mudler@mgh.harvard.edu.ORCID 0000-0003-3824-9162
Broad Institute · USNational Institute of Genomic Medicine · MXKorea National Institute of Health · KRNational University of Singapore · SGBoston University · USChinese University of Hong Kong · HKUniversity of Copenhagen · DKUniversity of Helsinki · FICentre for Human Genetics · GBHelmholtz Zentrum München · DEUniversity of Maryland, Baltimore · USAlbert Einstein College of Medicine · USChild Health and Development Institute · USIcahn School of Medicine at Mount Sinai · USInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán · MXJackson Memorial Hospital · USKeck Hospital of USC · USKing's College London · GBThe University of Texas Health Science Center at Houston · USThe University of Texas Health Science Center at San Antonio · US
Funding
Stable Isotope and Metabolomics CoreP60DK020541 · NIDDK · YESHIVA UNIVERSITY · PI PESSIN, JEFFREY E. · 1986 to 2014
$29.8MTranslational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3MProposal for the AMP T2D-GENES Data Coordination Center and Web PortalU01DK105554 · NIDDK · BROAD INSTITUTE, INC. · PI FLOREZ, JOSE CARLOS · 2015 to 2019
$16.8MIdentifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6MTargeted Genetic Analysis of T2D and Quantitative TraitsR01DK072193 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2005 to 2026
$11.3MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MGenetic epidemiology of rare and regulatory variants for metabolic traitsR01DK093757 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2011 to 2026
$8.2MThe Child Heath Research CenterK12HD052896 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Wendy K Chung · 2007 to 2026
$7.9MIdentifying Genes for Type 2 Diabetes:FUSIONR01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2003 to 2025
$6.7MMethods for Genome-wide Association Studies in Admixed PopulationsR01HG006399 · NHGRI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI PRICE, ALKES L · 2011 to 2024
$6.3MIn vivo and in vitro rare coding variant analyses to identify modulations of the adipocyte differentiation pathway that affect T2D riskR01DK125490 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Jason Flannick · 2020 to 2026
$3.9MMedical Research Council MC_PC_13040Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MR/K007017/1Medical Research Council MR/M501633/1NHGRI NIH HHS R01 HG006399NHLBI NIH HHS R01 HL105756NICHD NIH HHS K12 HD052896NIDDK NIH HHS K23 DK114551NIDDK NIH HHS K24 DK110550NIDDK NIH HHS K99 DK127196NIDDK NIH HHS P30 DK020541NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P60 DK020541NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R01 DK072193NIDDK NIH HHS R01 DK093757NIDDK NIH HHS R01 DK125490NIDDK NIH HHS R56 DK062370NIDDK NIH HHS U01 DK062370NIDDK NIH HHS U01 DK105554NIDDK NIH HHS UM1 DK078616Wellcome Trust 212945/Z/18/Z
Abstract
Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.
Indexed as
AdultBiological Variation, PopulationBiomarkersDiabetes Mellitus, Type 2DyslipidemiasExomeGenetic Predisposition to DiseaseGenotypeHumansMultifactorial InheritancePenetranceRisk AssessmentBiomarkers
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