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Common genetic dete...
Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
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Wang, Thomas J (author)
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Zhang, Feng (author)
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Richards, J Brent (author)
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Kestenbaum, Bryan (author)
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van Meurs, Joyce B (author)
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Berry, Diane (author)
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Kiel, Douglas P (author)
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Streeten, Elizabeth A (author)
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- 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
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Koller, Daniel L (author)
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Peltonen, Leena (author)
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Cooper, Jason D (author)
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O'Reilly, Paul F (author)
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Houston, Denise K (author)
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Glazer, Nicole L (author)
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- Vandenput, Liesbeth, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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Peacock, Munro (author)
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Shi, Julia (author)
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Rivadeneira, Fernando (author)
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McCarthy, Mark I (author)
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Anneli, Pouta (author)
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de Boer, Ian H (author)
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Mangino, Massimo (author)
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Kato, Bernet (author)
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Smyth, Deborah J (author)
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Booth, Sarah L (author)
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Jacques, Paul F (author)
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Burke, Greg L (author)
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Goodarzi, Mark (author)
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Cheung, Ching-Lung (author)
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Wolf, Myles (author)
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Rice, Kenneth (author)
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Goltzman, David (author)
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Hidiroglou, Nick (author)
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Ladouceur, Martin (author)
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Wareham, Nicholas J (author)
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Hocking, Lynne J (author)
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Hart, Deborah (author)
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Arden, Nigel K (author)
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Cooper, Cyrus (author)
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Malik, Suneil (author)
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Fraser, William D (author)
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Hartikainen, Anna-Liisa (author)
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Zhai, Guangju (author)
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Macdonald, Helen M (author)
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Forouhi, Nita G (author)
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Loos, Ruth Jf (author)
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Reid, David M (author)
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Hakim, Alan (author)
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Dennison, Elaine (author)
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Liu, Yongmei (author)
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Power, Chris (author)
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Stevens, Helen E (author)
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Jaana, Laitinen (author)
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Vasan, Ramachandran S (author)
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Soranzo, Nicole (author)
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Bojunga, Jörg (author)
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Psaty, Bruce M (author)
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- Lorentzon, Mattias, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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Foroud, Tatiana (author)
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Harris, Tamara B (author)
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Hofman, Albert (author)
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- 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
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Cauley, Jane A (author)
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Uitterlinden, Andre G (author)
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Gibson, Quince (author)
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Järvelin, Marjo-Riitta (author)
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Karasik, David (author)
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Siscovick, David S (author)
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Econs, Michael J (author)
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Kritchevsky, Stephen B (author)
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Florez, Jose C (author)
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Todd, John A (author)
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Dupuis, Josee (author)
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Hyppönen, Elina (author)
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Spector, Timothy D (author)
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(creator_code:org_t)
- 2010
- 2010
- English.
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In: Lancet. - 1474-547X. ; 376:9736, s. 180-8
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https://doi.org/10.1...
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Abstract
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- 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).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- By the author/editor
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Wang, Thomas J
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Zhang, Feng
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Richards, J Bren ...
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Kestenbaum, Brya ...
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van Meurs, Joyce ...
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Berry, Diane
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show more...
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Kiel, Douglas P
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Streeten, Elizab ...
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Ohlsson, Claes, ...
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Koller, Daniel L
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Peltonen, Leena
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Cooper, Jason D
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O'Reilly, Paul F
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Houston, Denise ...
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Glazer, Nicole L
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Vandenput, Liesb ...
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Peacock, Munro
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Shi, Julia
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Rivadeneira, Fer ...
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McCarthy, Mark I
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Anneli, Pouta
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de Boer, Ian H
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Mangino, Massimo
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Kato, Bernet
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Smyth, Deborah J
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Booth, Sarah L
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Jacques, Paul F
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Burke, Greg L
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Goodarzi, Mark
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Cheung, Ching-Lu ...
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Wolf, Myles
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Rice, Kenneth
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Goltzman, David
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Hidiroglou, Nick
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Ladouceur, Marti ...
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Wareham, Nichola ...
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Hocking, Lynne J
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Hart, Deborah
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Arden, Nigel K
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Cooper, Cyrus
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Malik, Suneil
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Fraser, William ...
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Hartikainen, Ann ...
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Zhai, Guangju
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Macdonald, Helen ...
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Forouhi, Nita G
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Loos, Ruth Jf
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Reid, David M
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Hakim, Alan
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Dennison, Elaine
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Liu, Yongmei
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Power, Chris
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Stevens, Helen E
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Jaana, Laitinen
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Vasan, Ramachand ...
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Soranzo, Nicole
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Bojunga, Jörg
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Psaty, Bruce M
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Lorentzon, Matti ...
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Foroud, Tatiana
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Harris, Tamara B
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Hofman, Albert
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Jansson, John-Ol ...
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Cauley, Jane A
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Uitterlinden, An ...
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Gibson, Quince
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Järvelin, Marjo- ...
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Karasik, David
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Siscovick, David ...
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Econs, Michael J
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Kritchevsky, Ste ...
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Florez, Jose C
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Todd, John A
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Dupuis, Josee
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Hyppönen, Elina
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Spector, Timothy ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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University of Gothenburg