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Cited by 1,540

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

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

Open access
Wang, Thomas J, Zhang, Feng, Richards, J Brent, Kestenbaum, Bryan, van Meurs, Joyce B, Berry, Diane, Kiel, Douglas P, Streeten, Elizabeth A, Ohlsson, Claes, Koller, Daniel L, Peltonen, Leena, Cooper, Jason D, O'Reilly, Paul F, Houston, Denise K, Glazer, Nicole L, Vandenput, Liesbeth, Peacock, Munro, Shi, Julia, Rivadeneira, Fernando, 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-Lung, Wolf, Myles, Rice, Kenneth, Goltzman, David, Hidiroglou, Nick, Ladouceur, Martin, Wareham, Nicholas J, Hocking, Lynne J, Hart, Deborah, Arden, Nigel K, Cooper, Cyrus, Malik, Suneil, Fraser, William D, Hartikainen, Anna-Liisa, Zhai, Guangju, Macdonald, Helen M, Forouhi, Nita G, Loos, Ruth JF, Reid, David M, Hakim, Alan, Dennison, Elaine, Liu, Yongmei, Power, Chris, Stevens, Helen E, Jaana, Laitinen, Vasan, Ramachandran S, Soranzo, Nicole, Bojunga, Jörg, Psaty, Bruce M, Lorentzon, Mattias, Foroud, Tatiana, Harris, Tamara B, Hofman, Albert, Jansson, John-Olov, Cauley, Jane A, Uitterlinden, Andre G, Gibson, Quince, Järvelin, Marjo-Riitta, Karasik, David, Siscovick, David S, Econs, Michael J, Kritchevsky, Stephen B, Florez, Jose C, Todd, John A, Dupuis, Josee, Hyppönen, Elina, Spector, Timothy D·2010·The Lancet
DOI 10.1016/s0140-6736(10)60588-0
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Abstract

Background Vitamin D is crucial for maintaining musculoskeletal health. Recently, vitamin D insufficiency has been linked to a number of extraskeletal disorders, including diabetes, cancer, and cardiovascular disease. Determinants of circulating 25-hydroxyvitamin D (25-OH D) include sun exposure and dietary intake, but its high heritability suggests that genetic determinants may also play a role. Methods We performed a genome-wide association study of 25-OH D among ∼30,000 individuals of European descent from 15 cohorts. Five cohorts were designated as discovery cohorts (n=16,125), five as in silico replication cohorts (n=9,366), and five as de novo replication cohorts (n=8,378). Association results were combined using z-score-weighted meta-analysis. Vitamin D insufficiency was defined as 25-OH D <75 nmol/L or <50 nmol/L. Findings Variants at three loci reached genome-wide significance in the discovery cohorts, and were confirmed in the replication cohorts: 4p12 (overall P=1.9 × 10-109 for rs2282679, in GC); 11q12 (P=2.1 × 10-27 for rs12785878, near DHCR7); 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). A genotype score was constructed using the three confirmed variants. Those in the top quartile of genotype scores had 2- to 2.5-fold elevated odds of vitamin D insufficiency (P≤1 × 10-26). Interpretation Variants near genes involved in cholesterol synthesis (DHCR7), hydroxylation (CYP2R1, CYP24A1), and vitamin D transport (GC) influence vitamin D status. Genetic variation at these loci identifies individuals of European descent who have substantially elevated risk of vitamin D insufficiency.

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Authors
Wang, T. J., Zhang, F., Richards, J. B., Kestenbaum, B., van Meurs, J. B., Berry, D., Kiel, D. P., Streeten, E. A., Ohlsson, C., Koller, D. L., Peltonen, L., Cooper, J. D., O'Reilly, P. F., Houston, D. K., Glazer, N. L., Vandenput, L., Peacock, M., Shi, J., Rivadeneira, F., McCarthy, M. I., Anneli, P., de Boer, I. H., Mangino, M., Kato, B., Smyth, D. J., Booth, S. L., Jacques, P. F., Burke, G. L., Goodarzi, M., Cheung, C.-L., Wolf, M., Rice, K., Goltzman, D., Hidiroglou, N., Ladouceur, M., Wareham, N. J., Hocking, L. J., Hart, D., Arden, N. K., Cooper, C., Malik, S., Fraser, W. D., Hartikainen, A.-L., Zhai, G., Macdonald, H. M., Forouhi, N. G., Loos, R. J., Reid, D. M., Hakim, A., Dennison, E., Liu, Y., Power, C., Stevens, H. E., Jaana, L., Vasan, R. S., Soranzo, N., Bojunga, J., Psaty, B. M., Lorentzon, M., Foroud, T., Harris, T. B., Hofman, A., Jansson, J.-O., Cauley, J. A., Uitterlinden, A. G., Gibson, Q., Järvelin, M.-R., Karasik, D., Siscovick, D. S., Econs, M. J., Kritchevsky, S. B., Florez, J. C., Todd, J. A., Dupuis, J., Hyppönen, E., & Spector, T. D.
Venue
The Lancet
Publisher
Elsevier BV
Published
2010-07
Volume
376
Issue
9736
Pages
180-188
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(10)60588-0
OpenAlex
W2162258804
Cited by
1,540
References
3
FWCI
73.46
Type
journal article
Language
en
Open access
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