University of Oulu

Jiang, X., O’Reilly, P., Aschard, H., Hsu, Y., Richards, J., Dupuis, J., Ingelsson, E., Karasik, D., Pilz, S., Berry, D., Kestenbaum, B., Zheng, J., Luan, J., Sofianopoulou, E., Streeten, E., Albanes, D., Lutsey, P., Yao, L., Tang, W., Econs, M., Wallaschofski, H., Völzke, H., Zhou, A., Power, C., McCarthy, M., Michos, E., Boerwinkle, E., Weinstein, S., Freedman, N., Huang, W., Van Schoor, N., van der Velde, N., Groot, L., Enneman, A., Cupples, L., Booth, S., Vasan, R., Liu, C., Zhou, Y., Ripatti, S., Ohlsson, C., Vandenput, L., Lorentzon, M., Eriksson, J., Shea, M., Houston, D., Kritchevsky, S., Liu, Y., Lohman, K., Ferrucci, L., Peacock, M., Gieger, C., Beekman, M., Slagboom, E., Deelen, J., Heemst, D., Kleber, M., März, W., de Boer, I., Wood, A., Rotter, J., Rich, S., Robinson-Cohen, C., den Heijer, M., Jarvelin, M., Cavadino, A., Joshi, P., Wilson, J., Hayward, C., Lind, L., Michaëlsson, K., Trompet, S., Zillikens, M., Uitterlinden, A., Rivadeneira, F., Broer, L., Zgaga, L., Campbell, H., Theodoratou, E., Farrington, S., Timofeeva, M., Dunlop, M., Valdes, A., Tikkanen, E., Lehtimäki, T., Lyytikäinen, L., Kähönen, M., Raitakari, O., Mikkilä, V., Ikram, M., Sattar, N., Jukema, J., Wareham, N., Langenberg, C., Forouhi, N., Gundersen, T., Khaw, K., Butterworth, A., Danesh, J., Spector, T., Wang, T., Hyppönen, E., Kraft, P., Kiel, D. (2018) Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nature Communications, 9 (1), 260. doi:10.1038/s41467-017-02662-2

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

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Author: Jiang, Xia1,2; O'Reilly, Paul F.3; Aschard, Hugues1,4;
Hsu, Yi-Hsiang5,6,7,8; Richards, J. Brent9,10,11,12; Dupuis, Josee13,14; Ingelsson, Erik15,16; Karasik, David5; Pilz, Stefan17; Berry, Diane18; Kestenbaum, Bryan19; Zheng, Jusheng20; Luan, Jianan20; Sofianopoulou, Eleni21; Streeten, Elizabeth A.22; Albanes, Demetrius23; Lutsey, Pamela L.24; Yao, Lu24; Tang, Weihong24; Econs, Michael J.25; Wallaschofski, Henri26,27; Voelzke, Henry27,28; Zhou, Ang29; Power, Chris18; McCarthy, Mark I.30,31,32; Michos, Erin D.33,34; Boerwinkle, Eric35; Weinstein, Stephanie J.23; Freedman, Neal D.23; Huang, Wen-Yi36; Van Schoor, Natasja M.37; van der Velde, Nathalie38,39; de Groot, Lisette C. P. G. M.40; Enneman, Anke38; Cupples, L. Adrienne13,14; Booth, Sarah L.41; Vasan, Ramachandran S.14; Liu, Ching-Ti13; Zhou, Yanhua13; Ripatti, Samuli42; Ohlsson, Claes43; Vandenput, Liesbeth43; Lorentzon, Mattias44,45; Eriksson, Johan G.46,47,48; Shea, M. Kyla41; Houston, Denise K.49; Kritchevsky, Stephen B.49; Liu, Yongmei50; Lohman, Kurt K.51; Ferrucci, Luigi52; Peacock, Munro25; Gieger, Christian53; Beekman, Marian54; Slagboom, Eline54; Deelen, Joris54,55; van Heemst, Diana56; Kleber, Marcus E.57; Maerz, Winfried57,58,59; de Boer, Ian H.60,61; Wood, Alexis C.62; Rotter, Jerome I.63,64; Rich, Stephen S.65,66; Robinson-Cohen, Cassianne67; den Heijer, Martin68; Järvelin, Marjo-Riitta69,70,71,72; Cavadino, Alana18,73; Joshi, Peter K.74; Wilson, James F.74,75; Hayward, Caroline75; Lind, Lars16; Michaelsson, Karl76; Trompet, Stella56,77; Zillikens, M. Carola68; Uitterlinden, Andre G.38,68; Rivadeneira, Fernando38,68; Broer, Linda68; Zgaga, Lina78; Campbell, Harry74,79; Theodoratou, Evropi74,79; Farrington, Susan M.79; Timofeeva, Maria79; Dunlop, Malcolm G.79; Valdes, Ana M.80,81; Tikkanen, Emmi82; Lehtimaki, Terho83,84; Lyytikainen, Leo-Pekka83,84; Kahonen, Mika85,86; Raitakari, Olli T.87,88; Mikkila, Vera89; Ikram, M. Arfan38; Sattar, Naveed90; Jukema, J. Wouter77,91; Wareham, Nicholas J.20; Langenberg, Claudia20; Forouhi, Nita G.20; Gundersen, Thomas E.92; Khaw, Kay-Tee21; Butterworth, Adam S.21; Danesh, John21,93; Spector, Timothy80; Wang, Thomas J.94; Hypponen, Elina18,29; Kraft, Peter1; Kiel, Douglas P.5,6,7,8
Organizations: 1Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Dept Epidemiol, 677 Huntington Ave, Boston, MA USA.
2Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Nobels Vagen 13, S-17177 Stockholm, Sweden.
3Kings Coll London, Inst Psychiat, Dept Social Genet & Dev Psychiat, De Crespigny Pk, London SE5 8AF, England.
4Inst Pasteur, Ctr Bioinformat Biostat & Biol Integrat C3BI, F-75724 Paris, France.
5Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA.
6Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA.
7Harvard Med Sch, Boston, MA 02115 USA.
8Broad Inst Harvard & Massachusetts Inst Technol, Boston, MA 02142 USA.
9Dept Med, 3755 Cote Ste Catherine Rd,Suite H-413, Montreal, PQ H3T 1E2, Canada.
10Dept Human Genet, 3755 Cote Ste Catherine Rd,Suite H-413, Montreal, PQ H3T 1E2, Canada.
11Dept Epidemiol, 3755 Cote Ste Catherine Rd,Suite H-413, Montreal, PQ H3T 1E2, Canada.
12Dept Biostat, 3755 Cote Ste Catherine Rd,Suite H-413, Montreal, PQ H3T 1E2, Canada.
13Boston Univ, Dept Biostat, Sch Publ Hlth, Crosstown Ctr, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA.
14Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
15Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA.
16Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden.
17Med Univ Graz, Div Endocrinol & Diabetol, Dept Internal Med, Auenbruggerpl 15, A-8036 Graz, Austria.
18UCL, Populat Policy & Practice, Inst Child Hlth, Great Ormond St, London WC1E 6BT, England.
19Kidney Res Inst, Div Nephrol, 325 Ninth Ave, Seattle, WA 98104 USA.
20Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England.
21Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Worts Causeway, Cambridge CB1 8RN, England.
22Univ Maryland, Genet & Personalized Med Program, Sch Med, Howard Hall Room 567, Baltimore, MD 21201 USA.
23NCI, Metabol Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
24Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300S 2nd St,Suite 300, Minneapolis, MN 55454 USA.
25Indiana Univ, Dept Med, Endocrinol, 1120W Michigan St, Indianapolis, IN 46202 USA.
26Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17489 Greifswald, Germany.
27DZHK German Ctr Cardiovasc Res, Partner Site, D-13316 Greifswald, Germany.
28Univ Med Greifswald, Inst Community Med, SHIP Klinisch Epidemiol Forsch, Walther Rathenau Str 48, D-17475 Greifswald, Germany.
29Univ South Australia, Ctr Populat Hlth Res, Sansom Inst Hlth Res, Adelaide, SA 5001, Australia.
30Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Old Rd, Oxford OX3 7LJ, England.
31Univ Oxford, Wellcome Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.
32Churchill Hosp, Oxford NIHR Biomed Res Ctr, Old Rd, Oxford OX3 7LJ, England.
33Johns Hopkins Sch Med, Ciccarone Ctr Prevent Heart Dis, Div Cardiol, Baltimore, MD 21287 USA.
34Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
35Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
36NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
37Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam Publ Hlth Res Inst, Boelelaan 1089a, NL-1081 HV Amsterdam, Netherlands.
38Erasmus MC, Dept Epidemiol, Postbus 2040, NL-3000 CA Rotterdam, Netherlands.
39AMC, Internal Med, Dept Geriatr, POB 22700, NL-1100 DE Amsterdam, Netherlands.
40Wageningen Univ, Dept Human Nutr, POB 176700, NL-6708 AA Wageningen, Netherlands.
41Tufts Univ, Vitamin K Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
42Univ Helsinki, Stat & Translat Genet, Biomedicum, Tukholmankatu 8, Helsinki 2U, Finland.
43Univ Gothenburg, Dept Internal Med & Clin Nutr, Vita Straket 11, S-41345 Gothenburg, Sweden.
44Univ Gothenburg, Dept Geriatr Med, S-43180 Molndal, Sweden.
45Sahlgrens Univ Hosp, S-43180 Molndal, Sweden.
46Univ Helsinki, Dept Gen Practice & Primary Hlth Care, POB 20,Tukholmankatu 8 B, FIN-00014 Helsinki, Finland.
47Univ Helsinki, Helsinki Univ Hosp, POB 20,Tukholmankatu 8 B, FIN-00014 Helsinki, Finland.
48Univ Helsinki, Folkhalsan Res Ctr, POB 2000014, Helsinki, Finland.
49Wake Forest Sch Med, Sticht Ctr Healthy Aging & Alzheimers Prevent, Med Ctr Blvd, Winston Salem, NC 27157 USA.
50Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Med Ctr Blvd, Winston Salem, NC 27157 USA.
51Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA.
52NIA, Longitudinal Studies Sect, Intramural Res Program, NIH, Baltimore, MD 21225 USA.
53German Res Ctr Environm Hlth, Mol Epidemiol, AME, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
54Leiden Univ, Mol Epidemiol, Med Ctr, Einthovenweg 20, NL-2333 ZC Leiden, Netherlands.
55Max Planck Inst Biol Ageing, Joseph Stelzmann Str 9b, D-50931 Cologne, Germany.
56Leiden Univ, Gerontol & Geriatr, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.
57Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Rheumatol Endocrino, Theodor Kutzer Ufer1, D-68167 Mannheim, Germany.
58Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Auenbruggerpl 15, A-8036 Graz, Austria.
59SYNLAB Holding Deutschland GmbH, Gubener Str 39, D-86156 Augsburg, Germany.
60Univ Washington, Div Nephrol, 325 Ninth Ave, Seattle, WA 98104 USA.
61Univ Washington, Kidney Res Inst, 325 Ninth Ave, Seattle, WA 98104 USA.
62ARS, USDA, Childrens Nutr Res Ctr, 1100 Bates Ave, Houston, TX 77071 USA.
63Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA.
64Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA.
65Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
66Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
67Vanderbilt Univ, Div Nephrol, Dept Med, Med Ctr, 1161 21st Ave S, Nashville, TN 37232 USA.
68Erasmus MC, Dept Internal Med, Postbus 2040, NL-3000 CA Rotterdam, Netherlands.
69Imperial Coll London, Epidemiol & Biostat Sch Publ Hlth, 156 Norfolk Pl,St Marys Campus, London W2 1PG, England.
70Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Oulu 90014, Finland.
71Univ Oulu, Bioctr Oulu, POB 5000,Aapistie 5A, FI-90014 Oulu, Finland.
72Oulu Univ Hosp, Unit Primary Care, Kajaanintie 50 POB 20,90029 OYS, FI-90220 Oulu, Finland.
73Queen Mary Univ London, Ctr Environm & Prevent Med, Wolfson Inst Prevent Med, Barts & London Sch Med & Dent, Charterhouse Sq, London EC1M 6BQ, England.
74Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland.
75Univ Edinburgh, MRC Inst Genet Mol Med, Western Gen Hosp, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
76Uppsala Univ, Dept Surg Sci, Dag Hammarskjoldsv 14 B,Uppsala Sci Pk, S-75185 Uppsala, Sweden.
77Leiden Univ, Dept Cardiol, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.
78Univ Dublin, Trinity Coll Dublin, Dept Publ Hlth & Primary Care, Inst Populat Hlth, D02 PN40, Dublin 24, Ireland.
79Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
80Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus,Westminster Bridge Rd, London SE1 7EH, England.
81Univ Nottingham, Sch Med, City Hosp, Hucknall Rd, Nottingham NG5 1PB, England.
82Univ Helsinki, FIMM Inst Mol Med Finland, POB 20, FI-00014 Helsinki, Finland.
83Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.
84Univ Tampere, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Tampere 33014, Finland.
85Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.
86Univ Tampere, Dept Clin Physiol, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Tampere 33014, Finland.
87Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.
88Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20014, Finland.
89Acad Finland, Hakaniemenranta 6,POB 131, FI-00531 Helsinki, Finland.
90BHF Glasgow Cardiovasc Res Ctr, Fac Med, Univ Ave, Glasgow G12 8QQ, Lanark, Scotland.
91Leiden Univ, Einthoven Lab Expt Vasc Med, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.
92Vitas AS, Gaustadaleen 21, N-0349 Oslo, Norway.
93Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.
94Vanderbilt Heart & Vasc Inst, Div Cardiovasc Med, 2220 Pierce Ave 383 Preston Res Bldg, Nashville, TN 37232 USA.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe201804106442
Language: English
Published: Springer Nature, 2018
Publish Date: 2018-04-10
Description:

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.

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Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 9
Article number: 260
DOI: 10.1038/s41467-017-02662-2
OADOI: https://oadoi.org/10.1038/s41467-017-02662-2
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Funding: 1958 British Birth Cohort (1958BC) The project was funded by the UK Medical Research Council (MRC) (project grant G0601653), and 25-hydroxyvitamin D assays by the BUPA foundation. EH is funded by a UK Department of Health Public Health Career Scientist Award. Use of DNA from this cohort was funded by MRC grant G0000934 and Wellcome Trust grant 068545/Z/02. This research used resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development, and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418. This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of investigators who contributed to generation of the data is available from the Wellcome Trust Case-Control Consortium website. Funding for the project was provided by the Wellcome Trust under award 076113. Great Ormond Street Hospital/University College London, Institute of Child Health receives a proportion of funding from the Department of Health’s NIHR (Biomedical Research Centres funding). MMcC is a Wellcome Trust Senior Investigator supported by Wellcome Trust awards 098381 and 090532. Cardiovascular Health Study (CHS) Research for this cohort that was reported in this article was supported by contract numbers N01-HC-85079 to N01-HC-85086, N01-HC-35129, N01 HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295, R01 HL084443, R01 HL087652, and R01 AG027002 from NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal investigators and institutions is available at the Cardiovascular Health Study website. DNA handling and genotyping was supported in part by National Center for Research Resources grant M01RR00069 to the Cedars-Sinai General Clinical Research Center Genotyping core and NIDDK grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Framingham Heart Study (FHS) Framingham Heart Study of the National Heart, Lung and Blood Institute (NHLBI) of the US National Institutes of Health (NIH) and Boston University School of Medicine is supported by the NIH/NHLBI contracts N01-HC-25195 and HHSN268201500001I. The present study received support from the American Heart Association, the US Department of Agriculture, Agricultural Research Service (under Cooperative Agreement No 58-1950-7-707), the National Institute of Aging (AG14759), the US National Institute for Arthritis, Musculoskeletal and Skin Diseases (R01AR057118), and the US National Institute for Arthritis, Musculoskeletal and Skin Diseases and National Institute on Aging (R01 AR 41398). DK was supported by a grant from the National Institute of Arthritis, Musculoskeletal, and Skin Diseases and the National Institute on Aging (R01 AR/AG 41398), and also by FP7-PEOPLE-2012-Marie Curie Career Integration Grants (CIG)). The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource project. This work was partly supported by a contract with Affymetrix Inc for genotyping services (Contract No N02-HL-6-4278). A portion of this research used the Linux Cluster for Genetic Analysis, which is funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Gothenberg Osteoporosis and Obesity Determinants (GOOD) Study Financial support was received from the Swedish Research Council, the Swedish Foundation for Strategic Research, The ALF/LUA research grant in Gothenburg, the Lundberg Foundation, the Emil and Vera Cornell Foundation, the Torsten and Ragnar S.derberg’s Foundation, Petrus and Augusta Hedlunds Foundation, the V.stra G.taland Foundation, the G.teborg Medical Society, and the Sahlgrenska Center for Cardiovascular and Metabolic Research (CMR, no A305:188), which is supported by the Swedish Strategic Foundation. Health, Aging and Body Composition Study (Health ABC) This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging and National Institute on Aging contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, NIA grant R01-AG028050, and NINR grant R01-NR012459. Assessment of 25-hydroxyvitamin D concentrations was funded by a National Institute on Aging grant, R01-AG029364. The genome-wide association study was funded by a National Institute on Aging grant, R01-AG032098, and genotyping services were provided by CIDR. CIDR is fully funded through a federal contract from NIH to The Johns Hopkins University (contract number HHSN268200782096C). Study of Indiana Women This work was supported by NIH grants P01 AG-18397, M01 RR-00750, and R01 AG-041517. Genotyping services were provided by CIDR. CIDR is fully funded through a federal contract from NIH to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. North Finland Birth Cohort 1966 (NFBC) We thank the late Professor Paula Rantakallio (launch of NFBC1966), Ms Outi Tornwall and Ms Minttu Jussila (DNA biobanking). The authors would like to acknowledge the contribution of the late Academician of Science Leena Peltonen. The NFBC resource has been supported by grants from the Academy of Finland (project grants 104781, 120315, 129269, 1114194, 24300796, Center of Excellence in Complex Disease Genetics and SALVE), University Hospital Oulu, Biocenter, University of Oulu, Finland (75617), NHLBI grant 5R01HL087679-02 (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), ENGAGE project and grant agreement HEALTH-F4-2007-201413, EU FP7 EurHEALTHAgeing -277849, the Medical Research Council, UK (G0500539, G0600705, G1002319, PrevMetSyn/SALVE) and the MRC, Centenary Early Career Award. H2020 DynaHEALTH (European Union’s Horizon 2020 research and innovation programme under grant agreement No 633595); Exposomic, Genomic and Epigenomic Approach to Prediction of Metabolic and Cardiorespiratory function and Ill-Health (EGEA), Academy of Finland, Grant No 285547; ALEC Study (funded by the European Union's Horizon 2020 Research and Innovation programme under grant agreement No. 633212); H2020 / Marie Skłodowska-Curie Actions, CAPICE (Marie Curie Grant agreement Number 721567); National Public Health Institute, Biomedicum Helsinki, Finland. The Amish Family Osteoporosis Study (OOA) was funded by a grant from the National Institute of Arthritis, Musculoskeletal and Skin Diseases (R01 AR46838). The Rotterdam Study The generation and management of GWAS genotype data for the Rotterdam Study (RS I, RS II, RS III) was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. The GWAS datasets are supported by the Netherlands Organization of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA), project nr. 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters, MSc, and Carolina Medina-Gomez, MSc, for their help in creating the GWAS database, and Karol Estrada, PhD, Yurii Aulchenko, PhD, and Carolina Medina-Gomez, PhD, for the creation and analysis of imputed data. We would like to thank Dr. Karol Estrada, Dr. Fernando Rivadeneira, Dr. Tobias A. Knoch, Marijn Verkerk, Anis Abuseiris, Dr. Linda Boer and Rob de Graaf (Erasmus MC Rotterdam, The Netherlands), for their help in creating and maintaining GRIMP. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are very grateful to the study participants, the staff from the Rotterdam Study (particularly L. Buist and J.H. van den Boogert) and the participating general practitioners and pharmacists. DSM Nutritional Products AG, Kaiseraugst, Switzerland provided funding for the assessment of vitamin D. TwinsUK was funded by the Wellcome Trust, Arthritis Research Campaign, European Community’s Seventh Framework Programme (FP7/2007-2013)/grant agreement HEALTH-F2-2008-201865-GEFOS and Seventh Framework Programme grant 200800 Treat OA /(FP7/2007-2013), ENGAGE project grant agreement HEALTH-F4-2007-201413, and the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254). The study also receives support from the UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London. TDS is an NIHR senior investigator. The project also received support from a Biotechnology and Biological Sciences Research Council project grant. (G20234). The authors acknowledge the funding and support of the National Eye Institute (NEI) via an NIH/Center for Inherited Disease Research (CIDR) genotyping project. We thank the staff from the Genotyping Facilities at the Wellcome Trust Sanger Institute for sample preparation, quality control, and genotyping; Le Centre National de Gnotypage, France, for genotyping; Duke University, NC, USA, for genotyping; and the Finnish Institute of Molecular Medicine, Finnish Genome Center, University of Helsinki. Genotyping was also done by CIDR as part of an NEI/NIH project grant. Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, and by U.S. Public Health Service contract HHSN261201500005C from the National Cancer Institute, Department of Health and Human Services. The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute (NCI), US National Institutes of Health (NIH), Department of Health and Human Services (DHHS). Atherosclerosis Risk in Communities (ARIC) Study ARIC’s contribution to this project was supported by NHLBI R01 HL103706 and contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; Office of Dietary Supplements grant number R01 HL103706-S1, National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The authors thank the staff and participants of the ARIC study for their important contributions. B-vitamins of the Prevention of Osteoporotic Fractures (B-PROOF) is supported and funded by The Netherlands Organization for Health Research and Development (ZonMw, Grant 6130.0031), the Hague; unrestricted grant from NZO (Dutch Dairy Association), Zoetermeer; MCO Health, Almere; NCHA (Netherlands Consortium Healthy Ageing) Leiden/ Rotterdam; Ministry of Economic Affairs, Agriculture and Innovation (project KB-15-004-003), the Hague; Wageningen University, Wageningen; VU University Medical Center, Amsterdam; Erasmus MC, Rotterdam. The authors gratefully thank all study participants, and all co-workers who helped to succeed this trial, especially P.H. in ‘t Veld, M. Hillen-Tijdink, A. Nicolaas-Merkus, N. Pliester, S. Oliai Araghi, and S. Smits. They also thank Professor Dr. H.A.P. Pols for obtaining funding. Leiden Longevity Study (LLS) has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2011) under grant agreement number 259679 (IDEAL). This study was financially supported by the Innovation-Oriented Research Program on Genomics (SenterNovem IGE05007), the Centre for Medical Systems Biology and the Netherlands Consortium for Healthy Ageing (grant 050-060-810), all in the framework of the Netherlands Genomics Initiative, Netherlands Organization for Scientific Research (NWO), by Unilever Colworth and by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007). Ludwigshafen Risk and Cardiovascular Health Study (LURIC) is supported by the 7th Framework Program (integrated project AtheroRemo, grant agreement number 201668 and RiskyCAD, grant agreement number 305739) of the European Union. The work of M.E.K. was supported by the German Federal Ministry of Education and Research (grant number 01EA1411A). Multi-Ethnic Study of Atherosclerosis (MESA) MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Support for the Mineral Metabolite dataset was provided by grant HL096875. The Nurses’ Health Study (NHS) is supported by NIH grants P01CA087969 and 5U01HG004399-2. XJ is supported by VetenskarpsRadet International Postdoc Grant. The Health Professionals Follow-up Study (HPFS) is supported by NIH grant P01CA055075. The American Cancer Society (ACS) study is supported by U01 CA098710. K.C.S. is supported by NIH Kirschstein-NRSA T32 ES016645-01. The genome-wide scans have been supported by the NCI, NIH, under contract N01-CO-12400. The Orkney Complex Disease Study (ORCADES) was supported by the Chief Scientist Office of the Scottish Government (CZB/4/276, CZB/4/710), the Royal Society, the MRC Human Genetics Unit quinquennial programme “QTL in Health and Disease”, Arthritis Research UK and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. We would like to acknowledge the invaluable contributions of the research nurses in Orkney, the administrative team in Edinburgh and the people of Orkney. Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) was supported by an investigator initiated grant obtained from Bristol-Myers Squibb. Professor Dr. J. W. Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). The Scottish Colorectal Cancer Study (SOCCS) The work was funded by grants from Cancer Research UK (C348/A3758, C348/A8896, C348/A18927); Scottish Government Chief Scientist Office (K/OPR/2/2/D333, CZB/4/94, CZB/4/449); Medical Research Council (G0000657-53203, MR/K018647/1); Centre Grant from CORE as part of the Digestive Cancer Campaign (http://www.corecharity.org.uk). We thank all the participants and all the recruitment teams and collaborators who make such studies possible. We acknowledge the excellent technical support from Marion Walker. We are grateful to Ruth Wilson, Donna Markie, and all those who continue to contribute to recruitment, data collection, and data curation for the Study of Colorectal Cancer in Scotland studies. We acknowledge the expert support on sample preparation from the Genetics Core of the Edinburgh Wellcome Trust Clinical Research Facility. The Young Finns Study (YFS) has been financially supported by the Academy of Finland: grants 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; and Diabetes Research Foundation of Finnish Diabetes Association. The expert technical assistance in the statistical analyses by Irina Lisinen is gratefully acknowledged. Helsinki Birth Cohort Study (HBCS) We thank all study participants as well as everybody involved in the Helsinki Birth Cohort Study (HBCS). HBCS was financially supported by Academy of Finland (grant no. 129369, 129907, 135072, 129255, and 126775), Finnish Foundation for Diabetes Research, Novo Nordisk Foundation, Signe and Ane Gyllenberg Foundation, Samfundet Folkhälsan, Finska Läkaresällskapet, Liv och Hälsa, European Commission within the 7th Framework Programme (DORIAN, grant agreement no. 278603), and European Union Horizon 2020 programme (DYNAHEALTH grant no. 633595). The EPIC-InterAct is supported by EU-FP6 EU FP6 programme (LSHM_CT_2006_037197); Medical Research Council Epidemiology Unit (MC_UU_12015/1); Cambridge Initiative (RG71466, SJAH/004); NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014). The EPIC-Norfolk study received grants from the Medical Research Council (G9502233) and Cancer Research UK (SP2024-0201 and SP2024-0204). CHD case ascertainment and validation, genotyping, and clinical chemistry assays in EPIC-CVD were supported by grants awarded to the University of Cambridge from the EU Framework Programme 7 (HEALTH-F2-2012-279233), the UK Medical Research Council (G0800270) and British Heart Foundation (SP/09/002), and the European Research Council (268834).
EU Grant Number: (277849) EURHEALTHAGEING - European ResearcH on DevElopmentAL, BirtH and Genetic Determinants of Ageing
(633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
Academy of Finland Grant Number: 104781
120315
129269
1114194
24300796
285547
286284
134309
126925
121584
124282
129378
117787
41071
129369
129907
135072
129255
126775
Detailed Information: 104781 (Academy of Finland Funding decision)
120315 (Academy of Finland Funding decision)
129269 (Academy of Finland Funding decision)
1114194 (Academy of Finland Funding decision)
24300796 (Academy of Finland Funding decision)
285547 (Academy of Finland Funding decision)
286284 (Academy of Finland Funding decision)
134309 (Academy of Finland Funding decision)
126925 (Academy of Finland Funding decision)
121584 (Academy of Finland Funding decision)
124282 (Academy of Finland Funding decision)
129378 (Academy of Finland Funding decision)
117787 (Academy of Finland Funding decision)
41071 (Academy of Finland Funding decision)
129369 (Academy of Finland Funding decision)
129907 (Academy of Finland Funding decision)
135072 (Academy of Finland Funding decision)
129255 (Academy of Finland Funding decision)
126775 (Academy of Finland Funding decision)
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