Details

Autor(en) / Beteiligte

• Wang, Thomas J, MD
• Zhang, Feng, PhD
• Richards, J Brent, MD
• Kestenbaum, Bryan, MD
• van Meurs, Joyce B, PhD
• Berry, Diane, MSc
• Kiel, Douglas P, MD
• Streeten, Elizabeth A, MD
• Ohlsson, Claes, Prof
• Koller, Daniel L, PhD
• Peltonen, Leena, Prof
• Cooper, Jason D, PhD
• O'Reilly, Paul F, PhD
• Houston, Denise K, PhD
• Glazer, Nicole L, PhD
• Vandenput, Liesbeth, PhD
• Peacock, Munro, Prof
• Shi, Julia, MSc
• Rivadeneira, Fernando, PhD
• McCarthy, Mark I, Prof
• Anneli, Pouta, PhD
• de Boer, Ian H, MD
• Mangino, Massimo, PhD
• Kato, Bernet, PhD
• Smyth, Deborah J, BSc
• Booth, Sarah L, Prof
• Jacques, Paul F, ScD
• Burke, Greg L, Prof
• Goodarzi, Mark, Prof
• Cheung, Ching-Lung, PhD
• Wolf, Myles, MD
• Rice, Kenneth, PhD
• Goltzman, David, Prof
• Hidiroglou, Nick, PhD
• Ladouceur, Martin, PhD
• Wareham, Nicholas J, Prof
• Hocking, Lynne J, PhD
• Hart, Deborah, PhD
• Arden, Nigel K, Prof
• Cooper, Cyrus, Prof
• Malik, Suneil, PhD
• Fraser, William D, Prof
• Hartikainen, Anna-Liisa, Prof
• Zhai, Guangju, PhD
• Macdonald, Helen M, PhD
• Forouhi, Nita G, FFPH
• Loos, Ruth JF, PhD
• Reid, David M, Prof
• Hakim, Alan, MA
• Dennison, Elaine, PhD
• Liu, Yongmei, PhD
• Power, Chris, Prof
• Stevens, Helen E, HNC
• Jaana, Laitinen, PhD
• Vasan, Ramachandran S, Prof
• Soranzo, Nicole, PhD
• Bojunga, Jörg, MD
• Psaty, Bruce M, Prof
• Lorentzon, Mattias, PhD
• Foroud, Tatiana, Prof
• Harris, Tamara B, MD
• Hofman, Albert, Prof
• Jansson, John-Olov, Prof
• Cauley, Jane A, PhD
• Uitterlinden, Andre G, Prof
• Gibson, Quince, MBA
• Järvelin, Marjo-Riitta, Prof
• Karasik, David, PhD
• Siscovick, David S, Prof
• Econs, Michael J, Prof
• Kritchevsky, Stephen B, Prof
• Florez, Jose C, PhD
• Todd, John A, Prof
• Dupuis, Josee, Prof
• Hyppönen, Elina, PhD
• Spector, Timothy D, Prof

Titel

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

Ist Teil von

• The Lancet (British edition), 2010-07, Vol.376 (9736), p.180-188

Ort / Verlag

Kidlington: Elsevier Ltd

Erscheinungsjahr

2010

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Summary 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=1·9×10−109 for rs2282679, in GC ); 11q12 (p=2·1×10−27 for rs12785878, near DHCR7 ); and 11p15 (p=3·3×10−20 for rs10741657, near CYP2R1 ). Variants at an additional locus (20q13, CYP24A1 ) were genome-wide significant in the pooled sample (p=6·0×10−10 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=2·3×10−48 ) or lower than 50 nmol/L (1·92, 1·70–2·16, p=1·0×10−26 ) 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).