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)
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
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] = Heidelberg University
42 University of Washington [Seattle]
43 USDA - United States Department of Agriculture
44 Harbor UCLA Medical Center [Torrance, Ca.]
45 University of Virginia
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]
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
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] = Heidelberg University
42 University of Washington [Seattle]
43 USDA - United States Department of Agriculture
44 Harbor UCLA Medical Center [Torrance, Ca.]
45 University of Virginia
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]
Hugues Aschard
- Function : Author
- PersonId : 1071662
- ORCID : 0000-0002-7554-6783
- IdRef : 139628924
Jusheng Zheng
- Function : Author
- PersonId : 807951
- ORCID : 0000-0001-6560-4890
Mika Kähönen
- Function : Author
- PersonId : 762620
- ORCID : 0000-0002-4510-7341
Naveed Sattar
- Function : Author
- PersonId : 762622
- ORCID : 0000-0002-1604-2593
Elina Hyppönen
Connectez-vous pour contacter l'auteur
- Function : Correspondent author
- PersonId : 1104484
Connectez-vous pour contacter l'auteur
Peter Kraft
Connectez-vous pour contacter l'auteur
- Function : Correspondent author
- PersonId : 1104485
Connectez-vous pour contacter l'auteur
Douglas P. Kiel
Connectez-vous pour contacter l'auteur
- Function : Correspondent author
- PersonId : 1104486
Connectez-vous pour contacter l'auteur
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.
Origin : Publication funded by an institution