Genome-wide Association Study for Vitamin D Levels Reveals 69 Independent Loci.

Female Gene-Environment Interaction Genome-Wide Association Study Humans Male Polymorphism, Single Nucleotide Vitamin D / analogs & derivatives
gene-environment interaction genetic correlation genome-wide association studies partitioned heritability pathway analysis rare variants vitamin D

Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
05 03 2020
Historique:
received: 08 11 2019
accepted: 22 01 2020
pubmed: 16 2 2020
medline: 6 5 2020
entrez: 16 2 2020
Statut: ppublish

Résumé

We aimed to increase our understanding of the genetic determinants of vitamin D levels by undertaking a large-scale genome-wide association study (GWAS) of serum 25 hydroxyvitamin D (25OHD). To do so, we used imputed genotypes from 401,460 white British UK Biobank participants with available 25OHD levels, retaining single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) > 0.1% and imputation quality score > 0.3. We performed a linear mixed model GWAS on standardized log-transformed 25OHD, adjusting for age, sex, season of measurement, and vitamin D supplementation. These results were combined with those from a previous GWAS including 42,274 Europeans. In silico functional follow-up of the GWAS results was undertaken to identify enrichment in gene sets, pathways, and expression in tissues, and to investigate the partitioned heritability of 25OHD and its shared heritability with other traits. Using this approach, the SNP heritability of 25OHD was estimated to 16.1%. 138 conditionally independent SNPs were detected (p value < 6.6 × 10

Identifiants

DOI: 10.1016/j.ajhg.2020.01.017 PMID: 32059762 PMC: PMC7058824
pubmed: 32059762
pii: S0002-9297(20)30017-3
doi: 10.1016/j.ajhg.2020.01.017
pmc: PMC7058824
pii:
doi:

Substances chimiques

Vitamin D 1406-16-2
25-hydroxyvitamin D A288AR3C9H

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

327-337

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : CIHR
Pays : Canada
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : Medical Research Council [UK]
ID : MC_UU_00011/1
Pays : International
Organisme : Medical Research Council [UK]
ID : MC_UU_12015/1
Pays : International
Organisme : Wellcome Trust
ID : 202802/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701603
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_12028
Pays : United Kingdom

Informations de copyright

Copyright © 2020 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Références

Apoptosis. 2006 Feb;11(2):151-9
pubmed: 16502254
Anticancer Res. 2009 Sep;29(9):3713-20
pubmed: 19667169
Diabetologia. 1999 Jan;42(1):51-4
pubmed: 10027578
Diabet Med. 2007 Feb;24(2):200-7
pubmed: 17257284
Bioinformatics. 2019 Nov 1;35(22):4851-4853
pubmed: 31233103
Neurol Genet. 2016 Sep 13;2(5):e97
pubmed: 27652346
Endocr Connect. 2013 Apr 12;2(2):87-95
pubmed: 23781324
Nat Commun. 2015 Jan 19;6:5890
pubmed: 25597830
Nutrients. 2019 Jan 02;11(1):
pubmed: 30609725
Sci Rep. 2019 Feb 27;9(1):2880
pubmed: 30814568
Genet Epidemiol. 2013 Nov;37(7):658-65
pubmed: 24114802
Nat Genet. 2010 Jul;42(7):570-5
pubmed: 20562874
Am J Clin Nutr. 2010 Dec;92(6):1393-8
pubmed: 20943799
Nat Rev Cancer. 2014 May;14(5):342-57
pubmed: 24705652
Lancet Diabetes Endocrinol. 2017 Dec;5(12):986-1004
pubmed: 29102433
Neurology. 2017 Apr 25;88(17):1623-1629
pubmed: 28356466
Diabetes Res. 1991 Mar;16(3):145-8
pubmed: 1666347
BMJ. 2014 Apr 01;348:g2035
pubmed: 24690624
Diabetologia. 2006 Dec;49(12):2847-52
pubmed: 17072585
Diabet Med. 1995 Jan;12(1):30-5
pubmed: 7712700
PLoS One. 2018 Dec 6;13(12):e0207677
pubmed: 30521541
Neurology. 2019 Mar 19;92(12):e1387-e1394
pubmed: 30770424
Int J Epidemiol. 2003 Feb;32(1):1-22
pubmed: 12689998
Diabetologia. 2004 Mar;47(3):451-462
pubmed: 14758446
Diabetes Care. 2009 Nov;32(11):1977-9
pubmed: 19675194
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Transl Psychiatry. 2019 Sep 5;9(1):219
pubmed: 31488809
Nat Genet. 2015 Nov;47(11):1236-41
pubmed: 26414676
Clin Chem. 2009 Jun;55(6):1163-70
pubmed: 19359534
Endocr Rev. 2019 Aug 1;40(4):1109-1151
pubmed: 30321335
Clin Gastroenterol Hepatol. 2019 Oct;17(11):2227-2235.e1
pubmed: 30716477
Drug Metab Dispos. 2018 Apr;46(4):367-379
pubmed: 29343609
PLoS Med. 2015 Aug 25;12(8):e1001866
pubmed: 26305103
BMC Med. 2018 Aug 14;16(1):142
pubmed: 30103784
Br J Dermatol. 2020 Jan;182(1):97-103
pubmed: 31218665
Cancer Epidemiol Biomarkers Prev. 2018 Dec;27(12):1462-1471
pubmed: 30072546
Am J Hum Genet. 2011 Jan 7;88(1):76-82
pubmed: 21167468
Nutrients. 2018 Sep 06;10(9):
pubmed: 30200567
Eur J Clin Nutr. 2009 Apr;63(4):458-64
pubmed: 18030310
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Nat Genet. 2015 Nov;47(11):1228-35
pubmed: 26414678
Proc Natl Acad Sci U S A. 2004 May 18;101(20):7711-5
pubmed: 15128933
Nutrients. 2018 Dec 15;10(12):
pubmed: 30558284
Nat Genet. 2015 Dec;47(12):1385-92
pubmed: 26523775
BMC Bioinformatics. 2010 May 28;11:288
pubmed: 20509871
Nat Rev Genet. 2010 Jul;11(7):499-511
pubmed: 20517342
J Bone Miner Res. 2001 Feb;16(2):371-8
pubmed: 11204437
Nature. 2018 Oct;562(7726):203-209
pubmed: 30305743
Transl Res. 2016 Dec;178:54-62.e6
pubmed: 27496319
PLoS Genet. 2019 Jan 22;15(1):e1007889
pubmed: 30668570
J Cell Mol Med. 2019 Mar;23(3):2268-2271
pubmed: 30637964
Hum Mol Genet. 2010 Jul 1;19(13):2739-45
pubmed: 20418485
Nat Genet. 2016 Nov;48(11):1443-1448
pubmed: 27694958
Int J Epidemiol. 2019 Oct 1;48(5):1425-1434
pubmed: 31518429
Am J Hum Genet. 2016 Mar 3;98(3):456-472
pubmed: 26924531
Nat Commun. 2018 Jan 17;9(1):260
pubmed: 29343764
Horm Metab Res. 2005 Nov;37(11):680-3
pubmed: 16308836
Nat Genet. 2018 Apr;50(4):621-629
pubmed: 29632380
Stroke. 2018 Oct;49(10):2508-2511
pubmed: 30355092
Eur J Epidemiol. 2019 Jan;34(1):57-66
pubmed: 30465296
Lancet. 2010 Jul 17;376(9736):180-8
pubmed: 20541252
Nutrients. 2019 May 16;11(5):
pubmed: 31100827
J Clin Endocrinol Metab. 2018 Sep 1;103(9):3267-3277
pubmed: 29947775
Diabetes Care. 2013 Jul;36(7):1842-50
pubmed: 23801797
Clin Rheumatol. 2012 Feb;31(2):199-202
pubmed: 22020389
Nat Genet. 2016 May;48(5):510-8
pubmed: 26974007
Nat Genet. 2019 Feb;51(2):258-266
pubmed: 30598549
Am J Hum Genet. 2017 Aug 3;101(2):227-238
pubmed: 28757204
Int J Epidemiol. 2019 Oct 1;48(5):1416-1424
pubmed: 30597039
Lancet. 2001 Nov 3;358(9292):1500-3
pubmed: 11705562

Auteurs

Despoina Manousaki (D)

Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.

Ruth Mitchell (R)

MRC Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK.

Tom Dudding (T)

MRC Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK; Bristol Dental School, University of Bristol, Bristol BS8 2BN, UK.

Simon Haworth (S)

MRC Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK; Bristol Dental School, University of Bristol, Bristol BS8 2BN, UK.

Adil Harroud (A)

Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.

Vincenzo Forgetta (V)

Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.

Rupal L Shah (RL)

MRC Epidemiology Unit, University of Cambridge, Cambridge CB2 0SL, UK.

Jian'an Luan (J)

MRC Epidemiology Unit, University of Cambridge, Cambridge CB2 0SL, UK.

Claudia Langenberg (C)

MRC Epidemiology Unit, University of Cambridge, Cambridge CB2 0SL, UK.

Nicholas J Timpson (NJ)

MRC Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK.

J Brent Richards (JB)

Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T 1E2, Canada; Department of Medicine, McGill University Montreal, QC H3G 1Y6, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada; Department of Twin Research and Genetic Epidemiology, King's College London, London WC2R 2LS, UK. Electronic address: brent.richards@mcgill.ca.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Phénotype › Interaction entre gènes et environnement › Genome-wide Association Study for Vitamin D...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genome-wide Association Study for Vitamin D...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genome-wide Association Study for Vitamin D...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Genome-wide Association Study for Vitamin D...
questionsmedicales.fr › Composés polycycliques › Composés à cycles fusionnés › Stéroïdes › Sécostéroïdes › Vitamine D › Genome-wide Association Study for Vitamin D...