Journal articles

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Xia Jiang ^{1, 2} Paul F. O'Reilly ³ Hugues Aschard ^{1, 4} Yi-Hsiang Hsu ^{5, 6, 7} J. Brent Richards ⁸ Josée Dupuis ^{9, 10} Erik Ingelsson ^{11, 12} David Karasik ⁵ Stefan Pilz ¹³ Diane Berry ¹⁴ Bryan Kestenbaum ¹⁵ Jusheng Zheng ¹⁶ Jianan Luan ¹⁶ Eleni Sofianopoulou ¹⁶ Elizabeth A. Streeten ¹⁷ Demetrius Albanes ¹⁸ Pamela L. Lutsey ¹⁹ Lu Yao ¹⁹ Weihong Tang ¹⁹ Michael J. Econs ²⁰ Henri Wallaschofski ^{21, 22} Henry Völzke ^{22, 21} Ang Zhou ²³ Chris Power ¹⁴ Mark I. Mccarthy ^{24, 25} Erin D. Michos ^{26, 27} Eric Boerwinkle ²⁸ Stephanie J. Weinstein ¹⁸ Neal D. Freedman ¹⁸ Wen-Yi Huang ¹⁸ Natasja M. van Schoor ²⁹ Nathalie van Der Velde ^{30, 31} Lisette C. P. G. M. de Groot ³² Anke Enneman ³⁰ L. Adrienne Cupples ^{9, 10} Sarah L. Booth ³³ Ramachandran S. Vasan ¹⁰ Ching-Ti Liu ⁹ Yanhua Zhou ⁹ Samuli Ripatti ³⁴ Claes Ohlsson ³⁵ Liesbeth Vandenput ³⁵ Mattias Lorentzon ^{35, 36} Johan G. Eriksson ³⁴ M. Kyla Shea ³³ Denise K. Houston ³⁷ Stephen B. Kritchevsky ³⁷ Yongmei Liu ³⁷ Kurt K. Lohman ³⁷ Luigi Ferrucci ¹⁸ Munro Peacock ²⁰ Christian Gieger ³⁸ Marian Beekman ³⁹ Eline Slagboom ³⁹ Joris Deelen ^{39, 40} Diana Van Heemst ³⁹ Marcus E. Kleber ⁴¹ Winfried März ^{41, 13} Ian H. de Boer ⁴² Alexis C. Wood ⁴³ Jerome I. Rotter ⁴⁴ Stephen S. Rich ⁴⁵ Cassianne Robinson-Cohen ⁴⁶ Martin den Heijer ³⁰ Marjo-Riitta Jarvelin ^{47, 48, 49} Alana Cavadino ^{14, 50} Peter K. Joshi ⁵¹ James F. Wilson ⁵¹ Caroline Hayward ⁵¹ Lars Lind ¹² Karl Michaëlsson ¹² Stella Trompet ³⁹ M. Carola Zillikens ³⁰ Andre G. Uitterlinden ³⁰ Fernando Rivadeneira ³⁰ Linda Broer ³⁰ Lina Zgaga ⁵² Harry Campbell ⁵¹ Evropi Theodoratou ⁵¹ Susan M. Farrington ⁵¹ Maria Timofeeva ⁵¹ Malcolm G. Dunlop ⁵¹ Ana M. Valdes ^{3, 53} Emmi Tikkanen ³⁴ Terho Lehtimäki ^{54, 55} Leo-Pekka Lyytikäinen ^{54, 55} Mika Kähönen ^{56, 55} Olli T. Raitakari ^{57, 58} Vera Mikkilä ⁵⁹ M. Arfan Ikram ³⁰ Naveed Sattar ⁶⁰ J. Wouter Jukema ³⁹ Nicholas J. Wareham ¹⁶ Claudia Langenberg ¹⁶ Nita G. Forouhi ¹⁶ Thomas E. Gundersen ⁶¹ Kay-Tee Khaw ¹⁶ Adam S. Butterworth ¹⁶ John Danesh ^{16, 62} Timothy Spector ³ Thomas J. Wang ⁶³ Elina Hyppönen ^{14, 23, *} Peter Kraft ^{1, *} Douglas P. Kiel ^{5, 6, 7, *}

* Corresponding author

1 Harvard T.H. Chan School of Public Health

2 Karolinska Institutet [Stockholm]

3 King‘s College London

4 C3BI - Centre de Bioinformatique, Biostatistique et Biologie Intégrative

5 Hebrew SeniorLife [Boston]

6 BIDMC - Beth Israel Deaconess Medical Center [Boston]

7 Broad Institute [Cambridge]

8 McGill University = Université McGill [Montréal, Canada]

9 School of Public Health [Boston]

10 Framingham Heart Study

11 Stanford University

12 Uppsala University

13 Medical University Graz

14 UCL - University College of London [London]

15 KRI - Kidney Research Institute [Seattle]

16 CAM - University of Cambridge [UK]

17 University of Maryland School of Medicine

18 NIH - National Institutes of Health [Bethesda]

19 UMN - University of Minnesota [Twin Cities]

20 IUPUI - Indiana University - Purdue University Indianapolis

21 Universität Greifswald - University of Greifswald

22 DZHK - German Center for Cardiovascular Research

23 University of South Australia [Adelaide]

24 University of Oxford [Oxford]

25 Churchill Hospital Oxford Centre for Haematology

26 Johns Hopkins University School of Medicine [Baltimore]

27 Johns Hopkins Bloomberg School of Public Health [Baltimore]

28 UTHealth - The University of Texas Health Science Center at Houston

29 VU University Medical Center [Amsterdam]

30 Erasmus MC - Erasmus University Medical Center [Rotterdam]

31 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]

32 WUR - Wageningen University and Research [Wageningen]

33 Tufts University [Medford]

34 Helsingin yliopisto = Helsingfors universitet = University of Helsinki

35 GU - University of Gothenburg

36 Sahlgrenska University Hospital [Gothenburg]

37 Wake Forest School of Medicine [Winston-Salem]

38 German Research Center for Environmental Health - Helmholtz Center München (GmbH)

39 Leiden University Medical Center (LUMC)

40 Max planck Institute for Biology of Ageing [Cologne]

41 Universität Heidelberg [Heidelberg]

42 University of Washington [Seattle]

43 USDA - US Department of Agriculture [Beltsville]

44 Harbor UCLA Medical Center [Torrance, Ca.]

45 University of Virginia [Charlottesville]

46 Vanderbilt University Medical Center [Nashville]

47 Imperial College London

48 University of Oulu

49 Oulu University Hospital [Oulu]

50 QMUL - Queen Mary University of London

51 University of Edinburgh

52 Trinity College Dublin

53 UON - University of Nottingham, UK

54 Fimlab Laboratories [Tampere, Finland]

55 University of Tampere [Finland]

56 Tampere University Hospital

57 TYKS - Turku University Hospital

58 University of Turku

59 Academy of Finland

60 BHF GCRC - British Heart Foundation Glasgow Cardiovascular Research Centre

61 Vitas Ltd

62 The Wellcome Trust Sanger Institute [Cambridge]

63 Vanderbilt University [Nashville]

Abstract : Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Genetics / Human genetics

Life Sciences [q-bio] / Santé publique et épidémiologie

Statistics [stat] / Methodology [stat.ME]

Statistics [stat] / Applications [stat.AP]

Computer Science [cs] / Bioinformatics [q-bio.QM]

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https://hal-pasteur.archives-ouvertes.fr/pasteur-03278560
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Submitted on : Monday, July 5, 2021 - 4:51:43 PM
Last modification on : Tuesday, May 3, 2022 - 6:26:04 PM
Long-term archiving on: : Wednesday, October 6, 2021 - 9:18:28 PM