Author
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JIANG, XIA - Harvard School Of Public Health |
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O'REILLY, PAUL - King'S College |
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ASCHARD, HUGUES - Harvard School Of Public Health |
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HSU, YI - Beth Israel Deaconess Medical Center |
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RICHARDS, J - Jewish General Hospital |
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DUPUIS, JOSEE - Boston University School Of Public Health |
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INGELSSON, ERIK - Stanford University School Of Medicine |
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KARASIK, DAVID - Hebrew Senior Life |
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PILZ, STEFAN - Medical University Of Graz |
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BERRY, DIANE - University College London |
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KESTENBAUM, BRYAN - University Of Washington |
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ZHENG, JUSHENG - University Of Cambridge |
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LUAN, JIANAN - University Of Cambridge |
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SOFIANOPOULOU, ELENI - University Of Cambridge |
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STREETEN, ELIZABETH - University Of Maryland School Of Medicine |
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ALBANES, DEMETRIUS - National Cancer Institute (NCI, NIH) |
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LUTSEY, PAMELA - University Of Minnesota |
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YAO, LU - University Of Minnesota |
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TANG, WEIHONG - University Of Minnesota |
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ECONS, MICHAEL - Indiana University |
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WALLASCHOFSKI, HENRI - University Of Greifswald |
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VOLZKE, HENRY - University Of Greifswald |
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ZHOU, ANG - University Of South Australia |
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POWER, CHRIS - University College London |
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MCCARTHY, MARK - University Of Oxford |
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MICHOS, ERIN - Johns Hopkins University School Of Medicine |
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BOERWINKLE, ERIC - University Of Texas Health Science Center |
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WEINSTEIN, STEPHANIE - National Cancer Institute (NCI, NIH) |
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FREEDMAN, NEAL - National Cancer Institute (NCI, NIH) |
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HUANG, WEN - National Cancer Institute (NCI, NIH) |
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VAN SCHOOR, NATASJA - Vu University Medical Center |
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VAN DER VELDE, NATHALIE - Erasmus Medical Center |
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DE GROOT, LISETTE - Wageningen University |
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ENNEMAN, ANKE - Erasmus Medical Center |
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CUPPLES, L - Boston University School Of Public Health |
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BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University |
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VASAN, RAMACHANDRAN - Framingham Heart Study |
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LIU, CHING - Boston University School Of Public Health |
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ZHOU, YANHUA - Boston University School Of Public Health |
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RIPATTI, SAMULI - University Of Helsinki |
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OHLSSON, CLAES - University Of Gothenburg |
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VANDEPUT, LIESBETH - University Of Gothenburg |
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LORENTZON, MATTIAS - University Of Gothenburg |
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ERIKSSON, JOHAN - University Of Helsinki |
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SHEA, M - Jean Mayer Human Nutrition Research Center On Aging At Tufts University |
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HOUSTON, DENISE - Wake Forest School Of Medicine |
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KRITSHEVSKY, STEPHEN - Wake Forest School Of Medicine |
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LIU, YONGMEI - Wake Forest School Of Medicine |
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LOHMAN, KURT - Wake Forest School Of Medicine |
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FERUCCI, LUIGI - National Institute On Aging (NIA, NIH) |
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PEACOCK, MUNRO - Indiana University |
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GIEGER, CHRISTIAN - German Research Center For Environmental Health |
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BEEKMAN, MARIAN - Leiden University Medical Center |
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SLAGBOOM, ELINE - Leiden University Medical Center |
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DEELEN, JORIS - Leiden University Medical Center |
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VAN HEEMST, DIANA - Leiden University Medical Center |
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KLEBER, MARCUS - University Of Heidelberg |
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MARZ, WINFRIED - University Of Heidelberg |
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DE BOER, IAN - University Of Washington |
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WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC) |
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ROTTER, JEROME - Harbor-Ucla Medical Center |
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RICH, STEPHEN - University Of Virginia |
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ROBINSON-COHEN, CASSIANNE - Vanderbilt University Medical Center |
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DEN HEIJER, MARTIN - Erasmus Medical Center |
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JARVELIN, MARJO - Imperial College |
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CAVADINO, ALANA - University College London |
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JOSHI, PETER - University Of Edinburgh |
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WILSON, JAMES - University Of Edinburgh |
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HAYWARD, CAROLINE - University Of Edinburgh |
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LIND, LARS - Uppsala University |
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MICHAELSSON, KARL - Uppsala University |
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TROMPET, STELLA - Leiden University Medical Center |
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ZILLIKENS, M - Erasmus Medical Center |
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UITTERLINDEN, ANDRE - Erasmus Medical Center |
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RIVADENEIRA, FERNANDO - Erasmus Medical Center |
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BROER, LINDA - Erasmus Medical Center |
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ZGAGA, LINA - University Of Dublin |
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CAMPBELL, HARRY - University Of Edinburgh |
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THEODORATOU, EVROPI - University Of Edinburgh |
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FARRINGTON, SUSAN - University Of Edinburgh |
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TIMOFEEVA, MARIA - University Of Edinburgh |
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DUNLOP, MALCOM - University Of Edinburgh |
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VALDES, ANA - University Of Nottingham |
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TIKKANEN, EMMI - University Of Helsinki |
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LEHTIMAKI, TERHO - University Of Tampere |
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LYYTIKAINEN, LEO - University Of Tampere |
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KAHONEN, MIKA - Tampere University Hospital |
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RAITAKARI, OLLI - University Of Turku |
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WANG, THOMAS - Vanderbilt University Medical Center |
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HYPPONEN, ELENA - University College London |
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KRAFT, PETER - Harvard School Of Public Health |
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KIEL, DOUGLAS - Hebrew Senior Life |
Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 12/15/2017 Publication Date: 1/17/2018 Citation: Jiang, X., O'Reilly, P.F., Aschard, H., Hsu, Y.H., Richards, J.B., Dupuis, J., Ingelsson, E., Karasik, D., Pilz, S., Berry, D., Kestenbaum, B., Zheng, J., Luan, J., Sofianopoulou, E., Streeten, E.A., Albanes, D., Lutsey, P.L., Yao, L., Tang, W., Econs, M.J., Wallaschofski, H., Volzke, H., Zhou, A., Power, C., McCarthy, M.I., Michos, E.D., Boerwinkle, E., Weinstein, S.J., Freedman, N.D., Huang, W.Y., Van Schoor, N.M., van der Velde, N., de Groot, L.C., Enneman, A., Cupples, L.A., Booth, S.L., Vasan, R.S., Liu, C.T., Zhou, Y., Ripatti, S., Ohlsson, C., Vandeput, L., Lorentzon, M., Eriksson, J.G., Shea, M.K., Houston, D.K., Kritshevsky, S.B., Liu, Y., Lohman, K.K., Ferucci, L., Peacock, M., Gieger, C., Beekman, M., Slagboom, E., Deelen, J., van Heemst, D., Kleber, M.E., Marz, W., de Boer, I.H., Wood, A.C., Rotter, J.I., Rich, S.S., Robinson-Cohen, C., den Heijer, M., Jarvelin, M.R., Cavadino, A., Joshi, P.K., Wilson, J.F., Hayward, C., Lind, L., Michaelsson, K., Trompet, S., Zillikens, M.C., Uitterlinden, A.G., Rivadeneira, F., Broer, L., Zgaga, L., Campbell, H., Theodoratou, E., Farrington, S.M., Timofeeva, M., Dunlop, M.G., Valdes, A.M., Tikkanen, E., Lehtimaki, T., Lyytikainen, L.P., Kahonen, M., Raitakari, O.T., Wang, T.J., Hypponen, E., Kraft, P., Kiel, D.P. 2018. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nature Communications. 9:260. http://dx.doi.org/10.1038/s41467-017-02662-2. Interpretive Summary: Vitamin D deficiency has been linked to many health conditions, including obesity and its outcomes cardiovascular disease and cancer. Levels of Vitamin D in the blood are influenced by many factors including sun exposure, age, dietary intake of certain foods such as fortified dairy products and oily fish, supplements, and genetic factors, but the genetic reasons why some individuals have higher (better) levels of blood Vitamin D than others are poorly understood. To address this problem, we analyzed genetic variation across the whole genome to look for locations where genetic differences associate with differences in Vitamin D levels. We confirmed three known genetic loci, validated one suspected genetic locus, and identified two new genetic loci associated with Vitamin D levels. This work is of importance to other scientists who can use this information to identify the biological pathways explaining why some people have higher Vitamin D in their blood than others. Eventually, this subsequent information may help us design new interventions or therapeutic options for raising Vitamin D in the blood, which should be of interest to those at risk of obesity and cardiovascular disease, as well as their care providers. Technical 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. |