Transethnic Evaluation Identifies Low-Frequency Loci Associated With 25-Hydroxyvitamin D Concentrations

被引：27

作者：

Hong, Jaeyoung ^{[1
]}

Hatchell, Kathryn E. ^{[2
]}

Bradfield, Jonathan P. ^{[3
]}

Bjonnes, Andrew ^{[4
]}

Chesi, Alessandra ^{[5
]}

Lai, Chao-Qiang ^{[6
]}

Langefeld, Carl D. ^{[7
]}

Lu, Lingyi ^{[7
]}

Lu, Yingchang ^{[8
]}

Lutsey, Pamela L. ^{[9
]}

Musani, Solomon K. ^{[10
]}

Nalls, Mike A. ^{[11
,12
]}

Robinson-Cohen, Cassianne ^{[13
]}

Roizen, Jeffery D. ^{[3
,14
]}

Saxena, Richa ^{[4
]}

Tucker, Katherine L. ^{[15
]}

Ziegler, Julie T. ^{[7
]}

Arking, Dan E. ^{[16
]}

Bis, Joshua C. ^{[17
]}

Boerwinkle, Eric ^{[18
]}

Bottinger, Erwin P. ^{[8
]}

Bowden, Donald W. ^{[7
]}

Gilsanz, Vicente ^{[19
]}

Houston, Denise K. ^{[20
]}

Kalkwarf, Heidi J. ^{[21
]}

Kelly, Andrea ^{[5
,22
]}

Lappe, Joan M. ^{[23
]}

Liu, Yongmei ^{[24
]}

Michos, Erin D. ^{[25
]}

Oberfield, Sharon E. ^{[26
]}

Palmer, Nicholette D. ^{[7
]}

Rotter, Jerome I. ^{[27
,28
]}

Sapkota, Bishwa ^{[29
]}

Shepherd, John A. ^{[30
]}

Wilson, James G. ^{[31
]}

Basu, Saonli ^{[32
]}

de Boer, Ian H. ^{[13
]}

Divers, Jasmin ^{[7
]}

Freedman, Barry I. ^{[7
]}

Grant, Struan F. A. ^{[3
,14
,33
]}

Hakanarson, Hakon ^{[3
,33
]}

Harris, Tamara B. ^{[34
]}

Kestenbaum, Bryan R. ^{[13
]}

Kritchevsky, Stephen B. ^{[20
]}

Loos, Ruth J. F. ^{[8
,35
]}

Norris, Jill M. ^{[36
]}

Norwood, Arnita F. ^{[10
]}

Ordovas, Jose M. ^{[37
]}

Pankow, James S. ^{[9
]}

Psaty, Bruce M. ^{[17
,38
,39
,40
]}

机构：

[1] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA

[2] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53726 USA

[3] Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Genom, Philadelphia, PA 19104 USA

[4] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

[5] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[6] Tufts Univ, USDA ARS Human Nutr Res Ctr Aging, Boston, MA 02153 USA

[7] Wake Forest Sch Med, Winston Salem, NC 27109 USA

[8] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[9] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA

[10] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA

[11] Data Tecn Int, Glen Echo, MD 20812 USA

[12] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA

[13] Univ Washington, Dept Med, Div Nephrol, Kidney Res Inst, Seattle, WA 98195 USA

[14] Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA

[15] Univ Massachusetts, Dept Biomed & Nutr Sci, Lowell, MA 01854 USA

[16] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21210 USA

[17] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[18] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA

[19] Univ Southern Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dept Radiol, Los Angeles, CA USA

[20] Wake Forest Sch Med, Sect Gerontol & Geriatr Med, Dept Internal Med, Winston Salem, NC 27109 USA

[21] Cincinnati Childrens Hosp Med Ctr, Div Gastroenterol Hepatol & Nutr, Cincinnati, OH USA

[22] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[23] Creighton Univ, Omaha, NE 68178 USA

[24] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA

[25] Johns Hopkins Univ, Ciccarone Ctr Prevent Heart Dis, Sch Med, Baltimore, MD 21205 USA

[26] Columbia Univ, Med Ctr, Div Pediat Endocrinol Diabet & Metab, New York, NY 10027 USA

[27] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90095 USA

[28] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90095 USA

[29] Univ Oklahoma, Dept Pediat, Coll Med, Hlth Sci Ctr, Oklahoma City, OK 73104 USA

[30] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA

[31] Univ Mississippi, Dept Physiol & Biophys, Jackson, MS 39216 USA

[32] Univ Minnesota, Div Biostat, Minneapolis, MN 55455 USA

[33] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

[34] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA

[35] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA

[36] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO 80045 USA

[37] Tufts Univ, JM USDA Human Nutr Res Ctr Aging, Nutr & Genom, Boston, MA 02155 USA

[38] Univ Washington, Seattle, WA 98195 USA

[39] Univ Washington, Dept Epidemiol & Hlth Sci, Seattle, WA 98195 USA

[40] Kaiser Permanente Washington Hlth Res Inst, Seattle, WA 98101 USA

[41] Univ Oklahoma, Dept Pharmaceut Sci, Coll Pharm, Hlth Sci Ctr, Oklahoma City, OK 73117 USA

[42] Oklahoma Ctr Neurosci, Oklahoma City, OK 73104 USA

[43] Harvard Med Sch, Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02115 USA

[44] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA

[45] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA

[46] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[47] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA

[48] NorthShore Univ HealthSyst, Evanston, IL 60077 USA

[49] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2018年 / 103卷 / 04期

关键词：

VITAMIN-D SUPPLEMENTATION; GENOME-WIDE ASSOCIATION; RANDOMIZED CONTROLLED-TRIALS; D DEFICIENCY; MENDELIAN RANDOMIZATION; RACIAL DISPARITY; METAANALYSIS; RISK; CALCIUM; DISEASE;

D O I：

10.1210/jc.2017-01802

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Context: Vitamin D inadequacy is common in the adult population of the United States. Although the genetic determinants underlying vitamin D inadequacy have been studied in people of European ancestry, less is known about populations with Hispanic or African ancestry. Objective: The Trans-Ethnic Evaluation of Vitamin D (TRANSCEN-D) genomewide association study (GWAS) consortium was assembled to replicate genetic associations with 25-hydroxyvitamin D [25(OH) D] concentrations from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) meta-analyses of European ancestry and to identify genetic variants related to vitamin D concentrations in African and Hispanic ancestries. Design: Ancestry-specific (Hispanic and African) and transethnic (Hispanic, African, and European) meta-analyses were performed with Meta-Analysis Helper software (METAL). Patients or Other Participants: In total, 8541 African American and 3485 Hispanic American (from North America) participants from 12 cohorts and 16,124 European participants from SUNLIGHT were included in the study. Main Outcome Measures: Blood concentrations of 25(OH) D were measured for all participants. Results: Ancestry-specific analyses in African and Hispanic Americans replicated single nucleotide polymorphisms (SNPs) in GC (2 and 4 SNPs, respectively). An SNP (rs79666294) near the KIF4B gene was identified in the African American cohort. Transethnic evaluation replicated GC and DHCR7 region SNPs. Additionally, the transethnic analyses revealed SNPs rs719700 and rs1410656 near the ANO6/ARID2 and HTR2A genes, respectively. Conclusions: Ancestry-specific and transethnic GWASs of 25(OH) D confirmed findings in GC and DHCR7 for African and Hispanic American samples and revealed findings near KIF4B, ANO6/ARID2, and HTR2A. The biological mechanisms that link these regions with 25(OH) D metabolism warrant further investigation.

引用

页码：1380 / 1392

页数：13

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