Common genetic determinants of vitamin D insufficiency: a genome-wide association study.

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Common genetic determinants of vitamin D insufficiency: a genome-wide association study.

Wang, Thomas J (author)

Zhang, Feng (author)

Richards, J Brent (author)

Kestenbaum, Bryan (author)

van Meurs, Joyce B (author)

Berry, Diane (author)

Kiel, Douglas P (author)

Streeten, Elizabeth A (author)

Ohlsson, Claes, 1965 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine

Koller, Daniel L (author)

Peltonen, Leena (author)

Cooper, Jason D (author)

O'Reilly, Paul F (author)

Houston, Denise K (author)

Glazer, Nicole L (author)

Vandenput, Liesbeth, 1974 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine

Peacock, Munro (author)

Shi, Julia (author)

Rivadeneira, Fernando (author)

McCarthy, Mark I (author)

Anneli, Pouta (author)

de Boer, Ian H (author)

Mangino, Massimo (author)

Kato, Bernet (author)

Smyth, Deborah J (author)

Booth, Sarah L (author)

Jacques, Paul F (author)

Burke, Greg L (author)

Goodarzi, Mark (author)

Cheung, Ching-Lung (author)

Wolf, Myles (author)

Rice, Kenneth (author)

Goltzman, David (author)

Hidiroglou, Nick (author)

Ladouceur, Martin (author)

Wareham, Nicholas J (author)

Hocking, Lynne J (author)

Hart, Deborah (author)

Arden, Nigel K (author)

Cooper, Cyrus (author)

Malik, Suneil (author)

Fraser, William D (author)

Hartikainen, Anna-Liisa (author)

Zhai, Guangju (author)

Macdonald, Helen M (author)

Forouhi, Nita G (author)

Loos, Ruth Jf (author)

Reid, David M (author)

Hakim, Alan (author)

Dennison, Elaine (author)

Liu, Yongmei (author)

Power, Chris (author)

Stevens, Helen E (author)

Jaana, Laitinen (author)

Vasan, Ramachandran S (author)

Soranzo, Nicole (author)

Bojunga, Jörg (author)

Psaty, Bruce M (author)

Lorentzon, Mattias, 1970 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine

Foroud, Tatiana (author)

Harris, Tamara B (author)

Hofman, Albert (author)

Jansson, John-Olov, 1954 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology

Cauley, Jane A (author)

Uitterlinden, Andre G (author)

Gibson, Quince (author)

Järvelin, Marjo-Riitta (author)

Karasik, David (author)

Siscovick, David S (author)

Econs, Michael J (author)

Kritchevsky, Stephen B (author)

Florez, Jose C (author)

Todd, John A (author)

Dupuis, Josee (author)

Hyppönen, Elina (author)

Spector, Timothy D (author)

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(creator_code:org_t)

2010
2010
English.
In: Lancet. - 1474-547X. ; 376:9736, s. 180-8

Related links:: https://gup.ub.gu.se...; show more...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).

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By the author/editor: Wang, Thomas J; Zhang, Feng; Richards, J Bren ...; Kestenbaum, Brya ...; van Meurs, Joyce ...; Berry, Diane; show more...; Kiel, Douglas P; Streeten, Elizab ...; Ohlsson, Claes, ...; Koller, Daniel L; Peltonen, Leena; Cooper, Jason D; O'Reilly, Paul F; Houston, Denise ...; Glazer, Nicole L; Vandenput, Liesb ...; Peacock, Munro; Shi, Julia; Rivadeneira, Fer ...; McCarthy, Mark I; Anneli, Pouta; de Boer, Ian H; Mangino, Massimo; Kato, Bernet; Smyth, Deborah J; Booth, Sarah L; Jacques, Paul F; Burke, Greg L; Goodarzi, Mark; Cheung, Ching-Lu ...; Wolf, Myles; Rice, Kenneth; Goltzman, David; Hidiroglou, Nick; Ladouceur, Marti ...; Wareham, Nichola ...; Hocking, Lynne J; Hart, Deborah; Arden, Nigel K; Cooper, Cyrus; Malik, Suneil; Fraser, William ...; Hartikainen, Ann ...; Zhai, Guangju; Macdonald, Helen ...; Forouhi, Nita G; Loos, Ruth Jf; Reid, David M; Hakim, Alan; Dennison, Elaine; Liu, Yongmei; Power, Chris; Stevens, Helen E; Jaana, Laitinen; Vasan, Ramachand ...; Soranzo, Nicole; Bojunga, Jörg; Psaty, Bruce M; Lorentzon, Matti ...; Foroud, Tatiana; Harris, Tamara B; Hofman, Albert; Jansson, John-Ol ...; Cauley, Jane A; Uitterlinden, An ...; Gibson, Quince; Järvelin, Marjo- ...; Karasik, David; Siscovick, David ...; Econs, Michael J; Kritchevsky, Ste ...; Florez, Jose C; Todd, John A; Dupuis, Josee; Hyppönen, Elina; Spector, Timothy ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

Articles in the publication: Lancet

By the university: University of Gothenburg

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Common genetic determinants of vitamin D insufficiency: a genome-wide association study.

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