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

Jaeyoung Hong, Kathryn E. Hatchell, Jonathan P. Bradfield, Andrew Bjonnes, Alessandra Chesi, Chao Qiang Lai, Carl D. Langefeld, Lingyi Lu, Yingchang Lu, Pamela L. Lutsey, Solomon K. Musani, Mike A. Nalls, Cassianne Robinson-Cohen, Jeffery D. Roizen, Richa Saxena, Katherine L. Tucker, Julie T. Ziegler, Dan E. Arking, Joshua C. Bis, Eric Boerwinkle & 40 others Erwin P. Bottinger, Donald W. Bowden, Vicente Gilsanz, Denise K. Houston, Heidi J. Kalkwarf, Andrea Kelly, Joan M. Lappe, Yongmei Liu, Erin D. Michos, Sharon E. Oberfield, Nicholette D. Palmer, Jerome I. Rotter, Bishwa Sapkota, John A. Shepherd, James G. Wilson, Saonli Basu, Ian H. De Boer, Jasmin Divers, Barry I. Freedman, Struan F.A. Grant, Hakon Hakanarson, Tamara B. Harris, Bryan R. Kestenbaum, Stephen B. Kritchevsky, Ruth J.F. Loos, Jill M. Norris, Arnita F. Norwood, Jose M. Ordovas, James S. Pankow, Bruce M. Psaty, Dharambir K. Sanghera, Lynne E. Wagenknecht, Babette S. Zemel, James Meigs, Josée Dupuis, Jose C. Florez, Thomas Wang, Ching Ti Liu, Corinne D. Engelman, Liana K. Billings

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1380-1392
Number of pages13
JournalJournal of Clinical Endocrinology and Metabolism
Volume103
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Polymorphism
Hispanic Americans
Vitamin D
Nucleotides
Single Nucleotide Polymorphism
African Americans
Meta-Analysis
Genes
Metabolism
Blood
North America
25-hydroxyvitamin D
Population
Software
Outcome Assessment (Health Care)

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Hong, J., Hatchell, K. E., Bradfield, J. P., Bjonnes, A., Chesi, A., Lai, C. Q., ... Billings, L. K. (2018). Transethnic Evaluation Identifies Low-Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations. Journal of Clinical Endocrinology and Metabolism, 103(4), 1380-1392. https://doi.org/10.1210/jc.2017-01802

Transethnic Evaluation Identifies Low-Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations. / Hong, Jaeyoung; Hatchell, Kathryn E.; Bradfield, Jonathan P.; Bjonnes, Andrew; Chesi, Alessandra; Lai, Chao Qiang; Langefeld, Carl D.; Lu, Lingyi; Lu, Yingchang; Lutsey, Pamela L.; Musani, Solomon K.; Nalls, Mike A.; Robinson-Cohen, Cassianne; Roizen, Jeffery D.; Saxena, Richa; Tucker, Katherine L.; Ziegler, Julie T.; Arking, Dan E.; Bis, Joshua C.; Boerwinkle, Eric; Bottinger, Erwin P.; Bowden, Donald W.; Gilsanz, Vicente; Houston, Denise K.; Kalkwarf, Heidi J.; Kelly, Andrea; Lappe, Joan M.; Liu, Yongmei; Michos, Erin D.; Oberfield, Sharon E.; Palmer, Nicholette D.; Rotter, Jerome I.; Sapkota, Bishwa; Shepherd, John A.; Wilson, James G.; Basu, Saonli; De Boer, Ian H.; Divers, Jasmin; Freedman, Barry I.; Grant, Struan F.A.; Hakanarson, Hakon; Harris, Tamara B.; Kestenbaum, Bryan R.; Kritchevsky, Stephen B.; Loos, Ruth J.F.; Norris, Jill M.; Norwood, Arnita F.; Ordovas, Jose M.; Pankow, James S.; Psaty, Bruce M.; Sanghera, Dharambir K.; Wagenknecht, Lynne E.; Zemel, Babette S.; Meigs, James; Dupuis, Josée; Florez, Jose C.; Wang, Thomas; Liu, Ching Ti; Engelman, Corinne D.; Billings, Liana K.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 103, No. 4, 01.04.2018, p. 1380-1392.

Research output: Contribution to journalArticle

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 2018, 'Transethnic Evaluation Identifies Low-Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations', Journal of Clinical Endocrinology and Metabolism, vol. 103, no. 4, pp. 1380-1392. https://doi.org/10.1210/jc.2017-01802
Hong, Jaeyoung ; Hatchell, Kathryn E. ; Bradfield, Jonathan P. ; Bjonnes, Andrew ; Chesi, Alessandra ; Lai, Chao Qiang ; Langefeld, Carl D. ; Lu, Lingyi ; Lu, Yingchang ; Lutsey, Pamela L. ; Musani, Solomon K. ; Nalls, Mike A. ; Robinson-Cohen, Cassianne ; Roizen, Jeffery D. ; Saxena, Richa ; Tucker, Katherine L. ; Ziegler, Julie T. ; Arking, Dan E. ; Bis, Joshua C. ; Boerwinkle, Eric ; Bottinger, Erwin P. ; Bowden, Donald W. ; Gilsanz, Vicente ; Houston, Denise K. ; Kalkwarf, Heidi J. ; Kelly, Andrea ; Lappe, Joan M. ; Liu, Yongmei ; Michos, Erin D. ; Oberfield, Sharon E. ; Palmer, Nicholette D. ; Rotter, Jerome I. ; Sapkota, Bishwa ; Shepherd, John A. ; Wilson, James G. ; Basu, Saonli ; De Boer, Ian H. ; Divers, Jasmin ; Freedman, Barry I. ; Grant, Struan F.A. ; Hakanarson, Hakon ; Harris, Tamara B. ; Kestenbaum, Bryan R. ; Kritchevsky, Stephen B. ; Loos, Ruth J.F. ; Norris, Jill M. ; Norwood, Arnita F. ; Ordovas, Jose M. ; Pankow, James S. ; Psaty, Bruce M. ; Sanghera, Dharambir K. ; Wagenknecht, Lynne E. ; Zemel, Babette S. ; Meigs, James ; Dupuis, Josée ; Florez, Jose C. ; Wang, Thomas ; Liu, Ching Ti ; Engelman, Corinne D. ; Billings, Liana K. / Transethnic Evaluation Identifies Low-Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations. In: Journal of Clinical Endocrinology and Metabolism. 2018 ; Vol. 103, No. 4. pp. 1380-1392.
@article{659a0587ab1641bda0e4ed340dda248e,
title = "Transethnic Evaluation Identifies Low-Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations",
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.",
author = "Jaeyoung Hong and Hatchell, {Kathryn E.} and Bradfield, {Jonathan P.} and Andrew Bjonnes and Alessandra Chesi and Lai, {Chao Qiang} and Langefeld, {Carl D.} and Lingyi Lu and Yingchang Lu and Lutsey, {Pamela L.} and Musani, {Solomon K.} and Nalls, {Mike A.} and Cassianne Robinson-Cohen and Roizen, {Jeffery D.} and Richa Saxena and Tucker, {Katherine L.} and Ziegler, {Julie T.} and Arking, {Dan E.} and Bis, {Joshua C.} and Eric Boerwinkle and Bottinger, {Erwin P.} and Bowden, {Donald W.} and Vicente Gilsanz and Houston, {Denise K.} and Kalkwarf, {Heidi J.} and Andrea Kelly and Lappe, {Joan M.} and Yongmei Liu and Michos, {Erin D.} and Oberfield, {Sharon E.} and Palmer, {Nicholette D.} and Rotter, {Jerome I.} and Bishwa Sapkota and Shepherd, {John A.} and Wilson, {James G.} and Saonli Basu and {De Boer}, {Ian H.} and Jasmin Divers and Freedman, {Barry I.} and Grant, {Struan F.A.} and Hakon Hakanarson and Harris, {Tamara B.} and Kestenbaum, {Bryan R.} and Kritchevsky, {Stephen B.} and Loos, {Ruth J.F.} and Norris, {Jill M.} and Norwood, {Arnita F.} and Ordovas, {Jose M.} and Pankow, {James S.} and Psaty, {Bruce M.} and Sanghera, {Dharambir K.} and Wagenknecht, {Lynne E.} and Zemel, {Babette S.} and James Meigs and Jos{\'e}e Dupuis and Florez, {Jose C.} and Thomas Wang and Liu, {Ching Ti} and Engelman, {Corinne D.} and Billings, {Liana K.}",
year = "2018",
month = "4",
day = "1",
doi = "10.1210/jc.2017-01802",
language = "English (US)",
volume = "103",
pages = "1380--1392",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Transethnic Evaluation Identifies Low-Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations

AU - Hong, Jaeyoung

AU - Hatchell, Kathryn E.

AU - Bradfield, Jonathan P.

AU - Bjonnes, Andrew

AU - Chesi, Alessandra

AU - Lai, Chao Qiang

AU - Langefeld, Carl D.

AU - Lu, Lingyi

AU - Lu, Yingchang

AU - Lutsey, Pamela L.

AU - Musani, Solomon K.

AU - Nalls, Mike A.

AU - Robinson-Cohen, Cassianne

AU - Roizen, Jeffery D.

AU - Saxena, Richa

AU - Tucker, Katherine L.

AU - Ziegler, Julie T.

AU - Arking, Dan E.

AU - Bis, Joshua C.

AU - Boerwinkle, Eric

AU - Bottinger, Erwin P.

AU - Bowden, Donald W.

AU - Gilsanz, Vicente

AU - Houston, Denise K.

AU - Kalkwarf, Heidi J.

AU - Kelly, Andrea

AU - Lappe, Joan M.

AU - Liu, Yongmei

AU - Michos, Erin D.

AU - Oberfield, Sharon E.

AU - Palmer, Nicholette D.

AU - Rotter, Jerome I.

AU - Sapkota, Bishwa

AU - Shepherd, John A.

AU - Wilson, James G.

AU - Basu, Saonli

AU - De Boer, Ian H.

AU - Divers, Jasmin

AU - Freedman, Barry I.

AU - Grant, Struan F.A.

AU - Hakanarson, Hakon

AU - Harris, Tamara B.

AU - Kestenbaum, Bryan R.

AU - Kritchevsky, Stephen B.

AU - Loos, Ruth J.F.

AU - Norris, Jill M.

AU - Norwood, Arnita F.

AU - Ordovas, Jose M.

AU - Pankow, James S.

AU - Psaty, Bruce M.

AU - Sanghera, Dharambir K.

AU - Wagenknecht, Lynne E.

AU - Zemel, Babette S.

AU - Meigs, James

AU - Dupuis, Josée

AU - Florez, Jose C.

AU - Wang, Thomas

AU - Liu, Ching Ti

AU - Engelman, Corinne D.

AU - Billings, Liana K.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85045476831&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045476831&partnerID=8YFLogxK

U2 - 10.1210/jc.2017-01802

DO - 10.1210/jc.2017-01802

M3 - Article

VL - 103

SP - 1380

EP - 1392

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 4

ER -