Meta-analysis2018

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

Hong J, Hatchell KE, Bradfield JP, Bjonnes A, Chesi A, Lai CQ, Langefeld CD, Lu L, Lu Y, Lutsey PL, Musani SK, Nalls MA, Robinson-Cohen C, Roizen JD, Saxena R, Tucker KL, Ziegler JT, Arking DE, Bis JC, Boerwinkle E, Bottinger EP, Bowden DW, Gilsanz V, Houston DK, Kalkwarf HJ, Kelly A, Lappe JM, Liu Y, Michos ED, Oberfield SE, Palmer ND, Rotter JI, Sapkota B, Shepherd JA, Wilson JG, Basu S, de Boer IH, Divers J, Freedman BI, Grant SFA, Hakanarson H, Harris TB, Kestenbaum BR, Kritchevsky SB, Loos RJF, Norris JM, Norwood AF, Ordovas JM, Pankow JS, Psaty BM, Sanghera DK, Wagenknecht LE, Zemel BS, Meigs J, Dupuis J, Florez JC, Wang T, Liu CT, Engelman CD, Billings LK

The Journal of clinical endocrinology and metabolism · 32 citations

How it was studied

Design: Meta-analysis (indexed by PubMed)
Studied in: People
Main outcome: Health markers and function

Who paid for it

Funding: Independent funding
Government: National Institutes of Health
Government: National Institute on Aging
Government: National Heart, Lung, and Blood Institute
Government: National Human Genome Research Institute
Government: National Institute of Nursing Research
Government: National Institute of General Medical Sciences
Government: National Institute of Diabetes and Digestive and Kidney Diseases
Government: National Institute of Environmental Health Sciences
Government: U.S. National Library of Medicine
Government: National Center for Research Resources
Government: National Center for Advancing Translational Sciences
Government: National Institute on Minority Health and Health Disparities
Government: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Government: NHGRI NIH HHS
Government: NHLBI NIH HHS
Government: NIEHS NIH HHS
Government: NICHD NIH HHS
Government: NIDDK NIH HHS
Government: NCATS NIH HHS
Government: NIA NIH HHS
Government: NCRR NIH HHS
Government: NIGMS NIH HHS
Government: NLM NIH HHS
Government: NINR NIH HHS
Government: NIH HHS
Grants: National Heart, Lung, and Blood Institute (HHSN268201 100012C); National Heart, Lung, and Blood Institute (HHSN268201300050C); National Heart, Lung, and Blood Institute (HHSN268201100007I); National Institute on Aging (P01-AG-023394); National Heart, Lung, and Blood Institute (N01 HC085086); National Center for Advancing Translational Sciences (UL-1TR000124); National Heart, Lung, and Blood Institute (R01 HL103706); National Heart, Lung, and Blood Institute (U01-HL0-80295); National Heart, Lung, and Blood Institute (HHSN268201100007C); National Center for Advancing Translational Sciences (UL1TR000077); National Heart, Lung, and Blood Institute (R01-HL-087652); National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK071891); National Heart, Lung, and Blood Institute (N01-HC095169); National Institute of General Medical Sciences (U54-GM-115428); National Heart, Lung, and Blood Institute (R01-HL059367); National Center for Advancing Translational Sciences (UL1-TR-000,040); Eunice Kennedy Shriver National Institute of Child Health and Human Development (K08 HD087964); National Heart, Lung, and Blood Institute (HHSN2682 01100008C); National Institute of Diabetes and Digestive and Kidney Diseases (K24DK080140); National Heart, Lung, and Blood Institute (R01-HL085251); National Heart, Lung, and Blood Institute (N01-HC-095165); National Heart, Lung, and Blood Institute (HH-SN-268201100006C); National Heart, Lung, and Blood Institute (HHSN268201100011C); National Heart, Lung, and Blood Institute (HHSN2682011-00005I); National Center for Research Resources (M0-1RR 007122); National Center for Advancing Translational Sciences (UL1-TR001079); National Institute on Aging (R01AG032098); National Heart, Lung, and Blood Institute (N01 HC085079); National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK082766); National Heart, Lung, and Blood Institute (N01 HC095163); National Heart, Lung, and Blood Institute (R01-HL120393); Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD076321); National Heart, Lung, and Blood Institute (N01 HC085083); National Institute on Aging (R01 AG 023629); National Heart, Lung, and Blood Institute (R01-HL086694); National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK078616); National Institute on Aging (P30AG017266); National Institute on Aging (R01-AG 028050); National Heart, Lung, and Blood Institute (HHSN2682011-00009I); National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK063491); National Heart, Lung, and Blood Institute (R56 HL124004); National Heart, Lung, and Blood Institute (N01 HC085080); National Heart, Lung, and Blood Institute (HHSN268201100005C); National Heart, Lung, and Blood Institute (HHSN 268200800007C); National Institutes of Health (1s10od018522-01); National Institute of Diabetes and Digestive and Kidney Diseases (U01DK078616); National Heart, Lung, and Blood Institute (N02 HL064278); National Heart, Lung, and Blood Institute (HHSN268201300048C); National Heart, Lung, and Blood Institute (HHSN268201100005G); National Center for Advancing Translational Sciences (UL1TR001881.); National Heart, Lung, and Blood Institute (HHSN268201100010C); National Heart, Lung, and Blood Institute (N01-HC-095159); National Heart, Lung, and Blood Institute (N01 HC095168); Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD056465); National Heart, Lung, and Blood Institute (U01 HL130114); National Heart, Lung, and Blood Institute (N01-HC-095162); National Heart, Lung, and Blood Institute (R01-HL096875); U.S. National Library of Medicine (T15LM007359); National Heart, Lung, and Blood Institute (R01 HL105756); National Institute of Diabetes and Digestive and Kidney Diseases (K12 DK094723); National Heart, Lung, and Blood Institute (N01-HC-095161); National Heart, Lung, and Blood Institute (HHSN268201100011I); National Heart, Lung, and Blood Institute (HHSN268201300049C); Eunice Kennedy Shriver National Institute of Child Health and Human Development (P 2CHD047873); National Heart, Lung, and Blood Institute (R01HL060919); National Heart, Lung, and Blood Institute (HHSN268201500003C); National Heart, Lung, and Blood Institute (HHSN26820150 0003I); National Center for Research Resources (UL1 RR025005.); National Heart, Lung, and Blood Institute (HHSN268201200036C); National Heart, Lung, and Blood Institute (HHSN26820 1100009C); National Heart, Lung, and Blood Institute (N01 HC095167); National Heart, Lung, and Blood Institute (P50-HL105185); National Heart, Lung, and Blood Institute (N01HC085082); National Institute on Aging (N01 AG062106); National Heart, Lung, and Blood Institute (R01HL061019); National Heart, Lung, and Blood Institute (N01-HC-095160); National Heart, Lung, and Blood Institute (N01 HC055222); National Heart, Lung, and Blood Institute (N01 HC095166); National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK-007-028); National Heart, Lung, and Blood Institute (N01 HC095164); National Heart, Lung, and Blood Institute (HHSN2682011-00008I); National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK085175); Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD058886); National Heart, Lung, and Blood Institute (R01-HL-103612); National Heart, Lung, and Blood Institute (N01 HC085081); National Human Genome Research Institute (U01HG007417); National Institute on Aging (R01-AG029364); National Institute of Environmental Health Sciences (P30ES013508); National Human Genome Research Institute (HHSN268200782096C); National Institute of Diabetes and Digestive and Kidney Diseases (K01 DK109019); National Heart, Lung, and Blood Institute (R01HL060944); National Institute on Aging (N01 AG062103); National Institute of Nursing Research (R01-NR-012459)); National Heart, Lung, and Blood Institute (R01 HL087641); National Human Genome Research Institute (U01-HG0-04402); National Institute on Aging (N01 AG062101); National Center for Advancing Translational Sciences (UL1TR001420)

Based on 25 listed funder(s).

Publication

Published: 2018-01-09 · J Clin Endocrinol Metab · vol. 103 · issue 4 · pp. 1380–1392
Publisher: Oxford University Press
Cited: 44 citations · more than 94% of similar papers · 3.8× the field average
Impact: Top 10% most cited in its field
References: 30 works
Access: Open access (repository copy)
Research areas: Vitamin D Research Studies · Genetic Associations and Epidemiology · Nutrition, Genetics, and Disease
Keywords: Single-nucleotide polymorphism, Vitamin D and neurology, Genetic genealogy, Ancestry-informative marker, Genome-wide association study, Context (archaeology), Genetic association, vitamin D deficiency, Vitamin D-binding protein, SNP, Population, Genetic admixture, Genetics, Population stratification, Biology, Medicine, Demography, Gene, Internal medicine, Genotype, Environmental health
MeSH: humans, vitamin d deficiency, vitamin d, body mass index, gene frequency, polymorphism, single nucleotide, adolescent, adult, aged, middle aged, child, united states, female, male, genome-wide association study, young adult, genetic loci, hispanic or latino, white people, black or african american

DOI ↗PubMed Central ↗OpenAlex ↗

60 authors

From US

Jaeyoung HongBoston University
Kathryn E. HatchellUniversity of Wisconsin–Madison
Jonathan P. BradfieldChildren's Hospital of Philadelphia
Andrew BjonnesMassachusetts General Hospital
Alessandra ChesiChildren's Hospital of Philadelphia
Chao‐Qiang LaiTufts University

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.

Abstract via Europe PMC. Copyright remains with the authors or publisher.

Read the full text ↗View on PubMed ↗

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