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Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.

Publication ,  Journal Article
Liu, C-T; Raghavan, S; Maruthur, N; Kabagambe, EK; Hong, J; Ng, MCY; Hivert, M-F; Lu, Y; An, P; Bentley, AR; Drolet, AM; Gaulton, KJ; Guo, X ...
Published in: Am J Hum Genet
July 7, 2016

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.

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Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

July 7, 2016

Volume

99

Issue

1

Start / End Page

56 / 75

Location

United States

Related Subject Headings

  • White People
  • Transcription Factors
  • Racial Groups
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Molecular Sequence Annotation
  • Male
  • Islets of Langerhans
  • Introns
  • Insulin Resistance
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, C.-T., Raghavan, S., Maruthur, N., Kabagambe, E. K., Hong, J., Ng, M. C. Y., … Meigs, J. B. (2016). Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet, 99(1), 56–75. https://doi.org/10.1016/j.ajhg.2016.05.006
Liu, Ching-Ti, Sridharan Raghavan, Nisa Maruthur, Edmond Kato Kabagambe, Jaeyoung Hong, Maggie C. Y. Ng, Marie-France Hivert, et al. “Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.Am J Hum Genet 99, no. 1 (July 7, 2016): 56–75. https://doi.org/10.1016/j.ajhg.2016.05.006.
Liu C-T, Raghavan S, Maruthur N, Kabagambe EK, Hong J, Ng MCY, et al. Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet. 2016 Jul 7;99(1):56–75.
Liu, Ching-Ti, et al. “Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.Am J Hum Genet, vol. 99, no. 1, July 2016, pp. 56–75. Pubmed, doi:10.1016/j.ajhg.2016.05.006.
Liu C-T, Raghavan S, Maruthur N, Kabagambe EK, Hong J, Ng MCY, Hivert M-F, Lu Y, An P, Bentley AR, Drolet AM, Gaulton KJ, Guo X, Armstrong LL, Irvin MR, Li M, Lipovich L, Rybin DV, Taylor KD, Agyemang C, Palmer ND, Cade BE, Chen W-M, Dauriz M, Delaney JAC, Edwards TL, Evans DS, Evans MK, Lange LA, Leong A, Liu J, Liu Y, Nayak U, Patel SR, Porneala BC, Rasmussen-Torvik LJ, Snijder MB, Stallings SC, Tanaka T, Yanek LR, Zhao W, Becker DM, Bielak LF, Biggs ML, Bottinger EP, Bowden DW, Chen G, Correa A, Couper DJ, Crawford DC, Cushman M, Eicher JD, Fornage M, Franceschini N, Fu Y-P, Goodarzi MO, Gottesman O, Hara K, Harris TB, Jensen RA, Johnson AD, Jhun MA, Karter AJ, Keller MF, Kho AN, Kizer JR, Krauss RM, Langefeld CD, Li X, Liang J, Liu S, Lowe WL, Mosley TH, North KE, Pacheco JA, Peyser PA, Patrick AL, Rice KM, Selvin E, Sims M, Smith JA, Tajuddin SM, Vaidya D, Wren MP, Yao J, Zhu X, Ziegler JT, Zmuda JM, Zonderman AB, Zwinderman AH, AAAG Consortium, CARe Consortium, COGENT-BP Consortium, eMERGE Consortium, MEDIA Consortium, Adeyemo A, Boerwinkle E, Ferrucci L, Hayes MG, Kardia SLR, Miljkovic I, Pankow JS, Rotimi CN, Sale MM, Wagenknecht LE, Arnett DK, Chen Y-DI, Nalls MA, MAGIC Consortium, Province MA, Kao WHL, Siscovick DS, Psaty BM, Wilson JG, Loos RJF, Dupuis J, Rich SS, Florez JC, Rotter JI, Morris AP, Meigs JB. Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet. 2016 Jul 7;99(1):56–75.
Journal cover image

Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

July 7, 2016

Volume

99

Issue

1

Start / End Page

56 / 75

Location

United States

Related Subject Headings

  • White People
  • Transcription Factors
  • Racial Groups
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Molecular Sequence Annotation
  • Male
  • Islets of Langerhans
  • Introns
  • Insulin Resistance