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J Clin Endocrinol Metab. 2018 Apr 1;103(4):1380-1392. doi: 10.1210/jc.2017-01802.

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

Author information

1
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
2
Department of Population Health Sciences, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.
3
Center for Applied Genomics, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
4
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts.
5
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
6
USDA-ARS Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
7
Wake Forest School of Medicine, Winston-Salem, North Carolina.
8
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
9
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota.
10
Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
11
Data Tecnica International, Glen Echo, Maryland.
12
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
13
Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington.
14
Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
15
Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts.
16
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
17
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.
18
University of Texas Health Science Center at Houston, Houston, Texas.
19
Department of Radiology, Children's Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.
20
Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
21
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
22
Perelman School of Medicine at University of Pennsylvania, Philadelphia, Pennsylvania.
23
Creighton University, Omaha, Nebraska.
24
Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
25
Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland.
26
Division of Pediatric Endocrinology, Diabetes and Metabolism, Columbia University Medical Center, New York, New York.
27
Institute for Translational Genomics and Population Sciences, Department of Pediatrics and Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
28
Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
29
University of California San Francisco School of Medicine, San Francisco, California.
30
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
31
Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota.
32
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
33
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland.
34
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
35
Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado.
36
Nutrition and Genomics, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
37
University of Washington and Department of Epidemiology and Health Sciences, University of Washington, Seattle, Washington.
38
Kaiser Permanente Washington Health Research Institute, Seattle, Washington.
39
Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
40
Oklahoma Center for Neuroscience, Oklahoma City, Oklahoma.
41
Division of General Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
42
National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts.
43
Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts.
44
Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, Massachusetts.
45
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
46
Vanderbilt University, Nashville, Tennessee.
47
NorthShore University HealthSystem, Evanston, Illinois.
48
University of Chicago Pritzker School of Medicine, Chicago, Illinois.

Abstract

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.

PMID:
29325163
PMCID:
PMC6276579
DOI:
10.1210/jc.2017-01802
[Indexed for MEDLINE]
Free PMC Article

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