Evidence map›Paper›PMID 30595373›Full record

ArticleAmerican journal of human genetics2019

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits.

Aldi T Kraja, Chunyu Liu, Jessica L Fetterman, Mariaelisa Graff, Christian Theil Have, Charles Gu, Lisa R Yanek, Mary F Feitosa, Dan E Arking, Daniel I Chasman and 142 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
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

78 citing papers in PubMed, 159 citations in OpenAlex.

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18 more citing papers are in PubMed but not listed here.

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

152 authors at 20 institutions in 11 countries.

Aldi T KrajaDivision of Statistical Genomics, Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63110, USA. Electronic address: aldikraja@wustl.edu.
Chunyu LiuDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Jessica L FettermanEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.
Mariaelisa GraffDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27516, USA.
Christian Theil HaveNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Charles GuDivision of Biostatistics, Washington University School of Medicine, St Louis, MO 63110, USA.
Lisa R YanekGeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Mary F FeitosaDivision of Statistical Genomics, Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
Dan E ArkingMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Kristin YoungDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27516, USA.
Symen LigthartDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam 3015 CE, the Netherlands.
W David HillCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Stefan WeissInterfaculty Institute for Genetics and Functional Genomics, University Medicine and University of Greifswald, Greifswald 17475, Germany.
Jian'an LuanMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.
Franco GiulianiniDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Ruifang Li-GaoDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
Fernando P HartwigPostgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas 96020-220, Brazil; MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.
Shiow J LinDivision of Statistical Genomics, Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
Lihua WangDivision of Statistical Genomics, Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
Tom G RichardsonMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.
Jie YaoInstitute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics, at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Eliana P FernandezDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam 3015 CE, the Netherlands.
Mohsen GhanbariDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam 3015 CE, the Netherlands.
Mary K WojczynskiDivision of Statistical Genomics, Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
Wen-Jane LeeDepartment of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan; Department of Social Work, Tunghai University, Taichung 407, Taiwan.
Maria ArgosDepartment of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, IL 60612, USA.
Sebastian M ArmasuDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Ruteja A BarveDepartment of Genetics, Washington University School of Medicine, St Louis, MO 63110, USA.
Kathleen A RyanSchool of Medicine, Division of Endocrinology, Diabetes and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Ping AnDivision of Statistical Genomics, Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
Thomas J BaranskiDivision of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
Suzette J BielinskiDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Donald W BowdenCenter for Diabetes Research, Wake Forest School of Medicine, Cincinnati, OH 45206, USA.
Ulrich BroeckelHuman and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Kaare ChristensenThe Danish Aging Research Center, University of Southern Denmark, Odense 5000, Denmark.
Audrey Y ChuDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Janie CorleyCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Simon R CoxCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Andre G UitterlindenDepartment of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, the Netherlands.
Fernando RivadeneiraDepartment of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, the Netherlands.
Cheryl D CroppSamford University McWhorter School of Pharmacy, Birmingham, Alabama, Translational Genomics Research Institute (TGen), Phoenix, AZ 35229, USA.
E Warwick DawDivision of Statistical Genomics, Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
Diana van HeemstDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
Lisa de las FuentesCardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
He GaoDepartment of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
Ioanna TzoulakiDepartment of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK; Department of Hygiene and Epidemiology, University of Ioannina, Ioannina 45110, Greece.
Tarunveer S AhluwaliaSteno Diabetes Center Copenhagen, Copenhagen 2820, Denmark.
Renée de MutsertDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
Leslie S EmeryDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
A Mesut ErzurumluogluDepartment of Health Sciences, University of Leicester, Leicester LE1 7RH, UK.
James A PerrySchool of Medicine, Division of Endocrinology, Diabetes and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Mao FuSchool of Medicine, Division of Endocrinology, Diabetes and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Nita G ForouhiMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.
Zhenglong GuDivision of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
Yang HaiInstitute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics, at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Sarah E HarrisCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Centre for Genomic and Experimental Medicine, Medical Genetics Section, University of Edinburgh, Edinburgh EH4 2XU, UK.
Gibran HemaniMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.
Steven C HuntDepartment of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA; Department of Genetic Medicine, Weill Cornell Medicine, PO Box 24144, Doha, Qatar.
Marguerite R IrvinDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Anna E JonssonNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Anne E JusticeDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27516, USA; Biomedical and Translational Informatics, Geisinger Health, Danville, PA 17822, USA.
Nicola D KerrisonMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.
Nicholas B LarsonDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Keng-Hung LinDepartment of Ophthalmology, Taichung Veterans General Hospital, Taichung 407, Taiwan.
Latisha D Love-GregoryGenomics & Pathology Services, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Rasika A MathiasGeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; GeneSTAR Research Program, Divisions of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Joseph H LeeTaub Institute for Research on Alzheimer disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
Matthias NauckInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
Raymond NoordamDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
Ken K OngMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.
James PankowUniversity of Minnesota School of Public Health, Division of Epidemiology and Community Health, Minneapolis, MN 55454, USA.
Amit PatkiDepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Alison PattieCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Astrid PetersmannInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
Qibin QiDepartment of Epidemiology & Population Health, Albert Einstein School of Medicine, Bronx, NY 10461, USA.
Rasmus Ribel-MadsenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark; Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark; The Danish Diabetes Academy, 5000 Odense, Denmark.
Rebecca RohdeDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27516, USA.
Kevin SandowInstitute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics, at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Theresia M SchnurrNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Tamar SoferDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
John M StarrCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Adele M TaylorCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany.
Nicholas J TimpsonMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.
Hugoline G de HaanDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
Yujie WangDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27516, USA.
Peter E WeekeDepartment of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark.
Christine WilliamsDivision of Statistical Genomics, Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
Hongsheng WuComputer Science and Networking, Wentworth Institute of Technology, Boston, MA 02115, USA.
Wei YangGenome Technology Access Center, Washington University School of Medicine, St Louis, MO 63110, USA.
Donglin ZengDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Daniel R WitteDepartment of Public Health, Section of Epidemiology, Aarhus University, Denmark, Danish Diabetes Academy, Odense University Hospital, 5000 Odense, Denmark.
Bruce S WeirDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Nicholas J WarehamMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.
Henrik VestergaardNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark; Steno Diabetes Center Copenhagen, Copenhagen 2820, Denmark.
Stephen T TurnerDivision of Nephrology and Hypertension, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55902, USA.
Christian Torp-PedersenDepartment of Health Science and Technology, Aalborg University Hospital, Aalborg 9220, Denmark.
Evie StergiakouliMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.
Wayne Huey-Herng SheuDivision of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan; Institute of Medical Technology, National Chung-Hsing University, Taichung 402, Taiwan; School of Medicine, National Defense Medical Center, Taipei 114, Taiwan; School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
Frits R RosendaalDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
M Arfan IkramDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam 3015 CE, the Netherlands.
Oscar H FrancoDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam 3015 CE, the Netherlands; Institute of Social and Preventive Medicine (ISPM), University of Bern, 3012 Bern, Switzerland.
Paul M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Thomas T PerlsDepartment of Medicine, Geriatrics Section, Boston University School of Medicine and Boston Medical Center, Boston, MA 02118, USA.
Oluf PedersenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Ellen A NohrResearch Unit for Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark.
Anne B NewmanDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Allan LinnebergDepartment of Clinical Experimental Research, Rigshospitalet, Copenhagen 2200, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark; The Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen 2000, Denmark.
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.
Tuomas O KilpeläinenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
Marit E JørgensenSteno Diabetes Center Copenhagen, Copenhagen 2820, Denmark.
Torben JørgensenResearch Centre for Prevention and Health, Glostrup Hospital, Glostrup 2600, Denmark; Department of Public Health, Faculty of Health Sciences, University of Copenhagen, Copenhagen 1014, Denmark; Faculty of Medicine, Aalborg University, Aalborg 9100, Denmark.
Thorkild I A SørensenNovo Nordisk Foundation Center for Basic Metabolic Research (Section of Metabolic Genetics) and Department of Public Health (Section on Epidemiology), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200N, Denmark.
Georg HomuthInterfaculty Institute for Genetics and Functional Genomics, University Medicine and University of Greifswald, Greifswald 17475, Germany.
Torben HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Mark O GoodarziDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Cramer ChristensenDepartment of Internal Medicine, Section of Endocrinology, Vejle Lillebaelt Hospital, 7100 Vejle, Denmark.
Yii-Der Ida ChenInstitute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics, at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Aravinda ChakravartiCenter for Complex Disease Genomics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ivan BrandslundDepartment of Clinical Biochemistry, Vejle Hospital, 7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, 5000 Odense C, Denmark.
Klaus BonnelykkeCopenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte & Naestved 2820, Denmark; Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Kent D TaylorInstitute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics, at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Santiago RodriguezMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol BS8 2BN, UK.
Gail DaviesCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Bernardo L HortaPostgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas 96020-220, Brazil.
Bharat ThyagarajanDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
D C RaoDivision of Biostatistics, Washington University School of Medicine, St Louis, MO 63110, USA.
Niels GrarupNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Victor G Davila-RomanCardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Gavin HudsonWellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
Xiuqing GuoInstitute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics, at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Donna K ArnettUniversity of Kentucky, College of Public Health, Lexington, KY 40508, USA.
Caroline HaywardMRC Human Genetics Unit, University of Edinburgh, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, UK.
Dhananjay VaidyaGeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands; Department of Public Health and Primary Care, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
Hemant K TiwariDepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Daniel LevyThe Framingham Heart Study, Framingham, MA, USA; The Population Sciences Branch, NHLBI/NIH, Bethesda, MD 20892, USA.
Ruth J F LoosCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Genetics of Obesity and Related Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Abbas DehghanDepartment of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
Paul ElliottDepartment of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
Afshan N MalikKing's College London, Department of Diabetes, School of Life Course, Faculty of Life Sciences and Medicine, London SE1 1NN, UK.
Robert A ScottMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.
Diane M BeckerGeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Mariza de AndradeDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Michael A ProvinceDivision of Statistical Genomics, Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
James B MeigsDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of General Internal Medicine, Massachusetts General Hospital, Boston 02114, MA, USA; Program in Medical and Population Genetics, Broad Institute, Boston, MA 02142, USA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics, at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Kari E NorthDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27516, USA. Electronic address: kari_north@unc.edu.
University of Copenhagen · DKUniversity of Edinburgh · GBWashington University in St. Louis · USLeiden University Medical Center · NLThe Lundquist Institute · USUniversity of Cambridge · GBUniversity of North Carolina at Chapel Hill · USErasmus MC · NLJohns Hopkins University · USUniversitätsmedizin Greifswald · DEUniversity of Bristol · GBBrigham and Women's Hospital · USMayo Clinic in Florida · USBoston University · USImperial College London · GBUniversity of Alabama at Birmingham · USUniversity of Maryland, Baltimore · USUniversity of Southern Denmark · DKCornell University · USSteno Diabetes Centers · DK

Funding

Tracking and Evaluation CoreU54GM115428 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI COMPRETTA, CAROLINE E. · 2016 to 2025
$38.2M
UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel · 2001 to 2026
$36.3M
Why is the prevalence of obesity so high in U.S. Southern States? Regional predictors of BMI and obesity treatment response.P30DK056336 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BARBARA A GOWER · 2000 to 2026
$31.9M
Washington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Dominic N Reeds · 1999 to 2026
$30.2M
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI Shuibing Chen · 2015 to 2026
$27.7M
University of Alabama at Birmingham's Diabetes Research CenterP30DK079626 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Kirk Michael Habegger · 2013 to 2026
$19.5M
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
Gene-Environment Interactions and Weight GainR01HD057194 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GORDON-LARSEN, PENNY, NORTH, KARI E. · 2008 to 2019
$5.9M
Common Genetic Variation and Quantitative Diabetes TraitsR01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2008 to 2014
$5.0M
Theoretical Population Genetics SupplementR01GM075091 · NIGMS · UNIVERSITY OF WASHINGTON · PI WEIR, BRUCE S. · 2006 to 2020
$4.7M
Rare Sequence Variation and Diabetes Quantitative TraitsU01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2015 to 2019
$3.6M
Mitochondrial DNA Copy Number and Genetic Variation in Coronary Heart DiseaseR01HL131573 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI ARKING, DAN E · 2016 to 2019
$3.2M
Biotechnology and Biological Sciences Research Council BB/F019394/1Medical Research Council G9815508Medical Research Council MC_PC_19009Medical Research Council MC_UU_00007/10Medical Research Council MC_UU_12015/1Medical Research Council MC_UU_12015/2Medical Research Council MC_UU_12015/5Medical Research Council MR/K002767/1Medical Research Council MR/L01341X/1Medical Research Council MR/L01632X/1Medical Research Council MR/R023484/1Medical Research Council MR/S003886/1NHLBI NIH HHS K01 HL143142NHLBI NIH HHS K99 HL130580NHLBI NIH HHS R00 HL130580NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL131573NIDDK NIH HHS K24 DK080140NIDDK NIH HHS P30 DK020541NIDDK NIH HHS P30 DK056336NIDDK NIH HHS P30 DK056341NIDDK NIH HHS P30 DK079626NIDDK NIH HHS R01 DK078616NIDDK NIH HHS U01 DK078616NIEHS NIH HHS P30 ES010126NIGMS NIH HHS R01 GM075091NIGMS NIH HHS U54 GM115428Wellcome Trust 208806/Z/17/ZWellcome Trust G906919
6 · The paper itself

Abstract

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E-04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E-03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E-06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.

Indexed as

AdipocytesBody Mass IndexCardiovascular DiseasesCohort StudiesDiabetes MellitusDNA, MitochondrialGenes, MitochondrialGenetic VariationGlucoseGlycated HemoglobinHumansInsulinMetabolismMitochondriaQuantitative Trait LociWaist-Hip RatioDNA, MitochondrialGlucoseGlycated HemoglobinInsulinBMIglucoseHbA1cHOMA-BHOMA-IRinsulinmitochondriamtDNAMT-nDNA candidate geneswaist-to-hip ratio

Identifiers

PMID30595373
PMCPMC6323610
OpenAlexW2908331360

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