ArticleNature communications2020
MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk.
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Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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27citing papers in PubMed, 1 pooled it
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
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- Causal genes for osteoporosis: Mendelian randomization analysis with multilayer xQTL data.Medicine · 2026Article
- Identification of ephrin-A1-EphA2 signalling as a potential target for fracture prevention.Nature communications · 2026Article
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- The Michigan Genomics Initiative: A biobank linking genotypes and electronic clinical records in Michigan Medicine patients.Cell genomics · 2023Article
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Authors and funding
27 authors at 6 institutions in 4 countries.
Ida SurakkaDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA.
Lars G FritscheDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA.ORCID 0000-0002-2110-1690
Wei ZhouProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA, 02142, USA.ORCID 0000-0001-7719-0859
Joshua BackmanRegeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA.
Jack A KosmickiRegeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA.
Haocheng LuDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA.ORCID 0000-0002-5740-8010
Ben BrumptonK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, NO-7491, Trondheim, Norway.
Jonas B NielsenDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA.ORCID 0000-0002-6654-2852
Maiken E GabrielsenK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, NO-7491, Trondheim, Norway.
Anne Heidi SkogholtK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, NO-7491, Trondheim, Norway.
Brooke WolfordDepartment of Computational Medicine and Bioinformatics, University of Michigan, Palmer Commons, 100 Washtenaw Avenue, Ann Arbor, MI, 48109, USA.ORCID 0000-0003-3153-1552
Sarah E GrahamDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA.ORCID 0000-0003-1271-2489
Y Eugene ChenDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA.
Seunggeun LeeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, 1415 Washington Heights, 1700 SPH I, Ann Arbor, MI, 48109, USA.ORCID 0000-0002-8097-3878
Hyun Min KangDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, 1415 Washington Heights, 1700 SPH I, Ann Arbor, MI, 48109, USA.
Arnulf LanghammerHUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Postboks 8905, N-7491, Levanger, Norway.
Siri ForsmoHUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Postboks 8905, N-7491, Levanger, Norway.
Bjørn O ÅsvoldK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, NO-7491, Trondheim, Norway.ORCID 0000-0003-3837-2101
Unnur StyrkarsdottirdeCODE genetics/Amgen, Inc., Sturlugata 8, 101, Reykjavik, Iceland.ORCID 0000-0001-8146-8278
Hilma HolmdeCODE genetics/Amgen, Inc., Sturlugata 8, 101, Reykjavik, Iceland.ORCID 0000-0002-9517-6636
Daniel GudbjartssondeCODE genetics/Amgen, Inc., Sturlugata 8, 101, Reykjavik, Iceland.ORCID 0000-0002-5222-9857
Kari StefanssondeCODE genetics/Amgen, Inc., Sturlugata 8, 101, Reykjavik, Iceland.
Aris BarasRegeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA.ORCID 0000-0002-6830-3396
Regeneron Genetics Center
Goncalo R AbecasisDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, 1415 Washington Heights, 1700 SPH I, Ann Arbor, MI, 48109, USA.
Kristian HveemK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, NO-7491, Trondheim, Norway. kristian.hveem@ntnu.no.
Cristen J WillerDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA. cristen@umich.edu.ORCID 0000-0001-5645-4966
Regeneron (United States) · USNorwegian University of Science and Technology · NOUniversity of Michigan · USdeCODE Genetics (Iceland) · ISBroad Institute · USWashtenaw Community College · US
Funding
University of Michigan Training Program in Genomic ScienceT32HG000040 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sebastian Zoellner · 1995 to 2026
$16.4MTraining Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8MStudies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5MUsing genetics to discover mechanisms of myocardial infarctionR01HL109946 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YUQING Eugene CHEN, Ida Liisa Surakka · 2011 to 2026
$8.9MThe Role of PPAR-gamma in Vascular Lesion FormationR01HL068878 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2002 to 2019
$7.6MUsing genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3MUsing Genetics to Inform Mechanism of Cardiovascular DiseaseR35HL135824 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILLER, CRISTEN J · 2017 to 2022
$5.4MThe Role of TM6SF2 in Cardiovascular DiseaseR01HL137214 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2017 to 2020
$2.2MLarge-scale human genetics to understand molecular mechanisms of atrial fibrillation and related traitsR01HL130705 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILLER, CRISTEN J · 2016 to 2016
$741kNHGRI NIH HHS T32 HG000040NHGRI NIH HHS T32 HG002295NHLBI NIH HHS R01 HL068878NHLBI NIH HHS R01 HL109946NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL127564NHLBI NIH HHS R01 HL130705NHLBI NIH HHS R01 HL137214NHLBI NIH HHS R35 HL135824
Abstract
A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset of the Nord-Trøndelag Health Study, followed by imputation in the remaining sample (N = 19,705), and identified ten known BMD loci. However, one previously unreported variant, LoF mutation in MEPE, p.(Lys70IlefsTer26, minor allele frequency [MAF] = 0.8%), was associated with decreased ultradistal forearm BMD (P-value = 2.1 × 10
Indexed as
Genetic Association StudiesAdultAgedAged, 80 and overBone DensityCohort StudiesComputational BiologyExtracellular Matrix ProteinsFemaleFractures, BoneGene FrequencyGenetic Predisposition to DiseaseGenetic TestingGenome, HumanGlycoproteinsHumansExtracellular Matrix ProteinsGlycoproteinsMEPE protein, humanPhosphoproteins
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