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Detection of genetic loci associated with plasma fetuin-A: a meta-analysis of genome-wide association studies from the CHARGE Consortium.

Publication ,  Journal Article
Jensen, MK; Jensen, RA; Mukamal, KJ; Guo, X; Yao, J; Sun, Q; Cornelis, M; Liu, Y; Chen, M-H; Kizer, JR; Djoussé, L; Siscovick, DS; Psaty, BM ...
Published in: Hum Mol Genet
June 1, 2017

Plasma fetuin-A is associated with type 2 diabetes, and AHSG, the gene encoding fetuin-A, has been identified as a susceptibility locus for diabetes and metabolic syndrome. Thus far, unbiased investigations of the genetic determinants of plasma fetuin-A concentrations have not been conducted. We searched for single nucleotide polymorphisms (SNPs) related to fetuin-A concentrations by a genome-wide association study in six population-based studies. We examined the association of fetuin-A levels with ∼ 2.5 million genotyped and imputed SNPs in 9,055 participants of European descent and 2,119 African Americans. In both ethnicities, the strongest associations were centered in a region with a high degree of LD near the AHSG locus. Among 136 genome-wide significant (P < 0.05 × 10-8) SNPs near the AHSG locus, the top SNP was rs4917 (P =1.27 × 10-303), a known coding SNP in exon 6 that is associated with a 0.06 g/l (∼13%) lower fetuin-A level. This variant alone explained 14% of the variation in fetuin-A levels. Analyses conditioned on rs4917 indicated that the strong association with the AHSG locus stems from additional independent associations of multiple variants among European Americans. In conclusion, levels of fetuin-A in plasma are strongly associated with SNPs in its encoding gene, AHSG, but not elsewhere in the genome. Given the strength of the associations observed for multiple independent SNPs, the AHSG gene is an example of a candidate locus suitable for additional investigations including fine mapping to elucidate the biological basis of the findings and further functional experiments to clarify AHSG as a potential therapeutic target.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

June 1, 2017

Volume

26

Issue

11

Start / End Page

2156 / 2163

Location

England

Related Subject Headings

  • alpha-2-HS-Glycoprotein
  • White People
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Metabolic Syndrome
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetics & Heredity
 

Citation

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Jensen, M. K., Jensen, R. A., Mukamal, K. J., Guo, X., Yao, J., Sun, Q., … Ix, J. H. (2017). Detection of genetic loci associated with plasma fetuin-A: a meta-analysis of genome-wide association studies from the CHARGE Consortium. Hum Mol Genet, 26(11), 2156–2163. https://doi.org/10.1093/hmg/ddx091
Jensen, Majken K., Richard A. Jensen, Kenneth J. Mukamal, Xiuqing Guo, Jie Yao, Qi Sun, Marilyn Cornelis, et al. “Detection of genetic loci associated with plasma fetuin-A: a meta-analysis of genome-wide association studies from the CHARGE Consortium.Hum Mol Genet 26, no. 11 (June 1, 2017): 2156–63. https://doi.org/10.1093/hmg/ddx091.
Jensen MK, Jensen RA, Mukamal KJ, Guo X, Yao J, Sun Q, et al. Detection of genetic loci associated with plasma fetuin-A: a meta-analysis of genome-wide association studies from the CHARGE Consortium. Hum Mol Genet. 2017 Jun 1;26(11):2156–63.
Jensen, Majken K., et al. “Detection of genetic loci associated with plasma fetuin-A: a meta-analysis of genome-wide association studies from the CHARGE Consortium.Hum Mol Genet, vol. 26, no. 11, June 2017, pp. 2156–63. Pubmed, doi:10.1093/hmg/ddx091.
Jensen MK, Jensen RA, Mukamal KJ, Guo X, Yao J, Sun Q, Cornelis M, Liu Y, Chen M-H, Kizer JR, Djoussé L, Siscovick DS, Psaty BM, Zmuda JM, Rotter JI, Garcia M, Harris T, Chen I, Goodarzi MO, Nalls MA, Keller M, Arnold AM, Newman AB, Hoogeveen RC, Rexrode KM, Rimm EB, Hu FB, Ramachandran VS, Katz R, Pankow JS, Ix JH. Detection of genetic loci associated with plasma fetuin-A: a meta-analysis of genome-wide association studies from the CHARGE Consortium. Hum Mol Genet. 2017 Jun 1;26(11):2156–2163.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

June 1, 2017

Volume

26

Issue

11

Start / End Page

2156 / 2163

Location

England

Related Subject Headings

  • alpha-2-HS-Glycoprotein
  • White People
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Metabolic Syndrome
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetics & Heredity