TY - JOUR
T1 - A meta-analysis of genome-wide association studies of growth differentiation factor-15 concentration in blood
AU - Jiang, Jiyang
AU - Thalamuthu, Anbupalam
AU - Ho, Jennifer E.
AU - Mahajan, Anubha
AU - Ek, Weronica E.
AU - Brown, David A.
AU - Breit, Samuel N.
AU - Wang, Thomas J.
AU - Gyllensten, Ulf
AU - Chen, Ming Huei
AU - Enroth, Stefan
AU - Januzzi, James L.
AU - Lind, Lars
AU - Armstrong, Nicola J.
AU - Kwok, John B.
AU - Schofield, Peter R.
AU - Wen, Wei
AU - Trollor, Julian N.
AU - Johansson, Åsa
AU - Morris, Andrew P.
AU - Vasan, Ramachandran S.
AU - Sachdev, Perminder S.
AU - Mather, Karen A.
N1 - Publisher Copyright:
© 2018 Jiang, Thalamuthu, Ho, Mahajan, Ek, Brown, Breit, Wang, Gyllensten, Chen, Enroth, Januzzi, Lind, Armstrong, Kwok, Schofield, Wen, Trollor, Johansson, Morris, Vasan, Sachdev and Mather.
PY - 2018/3/23
Y1 - 2018/3/23
N2 - Blood levels of growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1), have been associated with various pathological processes and diseases, including cardiovascular disease and cancer. Prior studies suggest genetic factors play a role in regulating blood MIC-1/GDF-15 concentration. In the current study, we conducted the largest genome-wide association study (GWAS) to date using a sample of ~5,400 community-based Caucasian participants, to determine the genetic variants associated with MIC-1/GDF-15 blood concentration. Conditional and joint (COJO), gene-based association, and gene-set enrichment analyses were also carried out to identify novel loci, genes, and pathways. Consistent with prior results, a locus on chromosome 19, which includes nine single nucleotide polymorphisms (SNPs) (top SNP, rs888663, p = 1.690 × 10-35), was significantly associated with blood MIC-1/GDF-15 concentration, and explained 21.47% of its variance. COJO analysis showed evidence for two independent signals within this locus. Gene-based analysis confirmed the chromosome 19 locus association and in addition, a putative locus on chromosome 1. Gene-set enrichment analyses showed that the"COPI-mediated anterograde transport" gene-set was associated with MIC-1/GDF15 blood concentration with marginal significance after FDR correction (p = 0.067). In conclusion, a locus on chromosome 19 was associated with MIC-1/GDF-15 blood concentration with genome-wide significance, with evidence for a new locus (chromosome 1). Future studies using independent cohorts are needed to confirm the observed associations especially for the chromosomes 1 locus, and to further investigate and identify the causal SNPs that contribute to MIC-1/GDF-15 levels.
AB - Blood levels of growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1), have been associated with various pathological processes and diseases, including cardiovascular disease and cancer. Prior studies suggest genetic factors play a role in regulating blood MIC-1/GDF-15 concentration. In the current study, we conducted the largest genome-wide association study (GWAS) to date using a sample of ~5,400 community-based Caucasian participants, to determine the genetic variants associated with MIC-1/GDF-15 blood concentration. Conditional and joint (COJO), gene-based association, and gene-set enrichment analyses were also carried out to identify novel loci, genes, and pathways. Consistent with prior results, a locus on chromosome 19, which includes nine single nucleotide polymorphisms (SNPs) (top SNP, rs888663, p = 1.690 × 10-35), was significantly associated with blood MIC-1/GDF-15 concentration, and explained 21.47% of its variance. COJO analysis showed evidence for two independent signals within this locus. Gene-based analysis confirmed the chromosome 19 locus association and in addition, a putative locus on chromosome 1. Gene-set enrichment analyses showed that the"COPI-mediated anterograde transport" gene-set was associated with MIC-1/GDF15 blood concentration with marginal significance after FDR correction (p = 0.067). In conclusion, a locus on chromosome 19 was associated with MIC-1/GDF-15 blood concentration with genome-wide significance, with evidence for a new locus (chromosome 1). Future studies using independent cohorts are needed to confirm the observed associations especially for the chromosomes 1 locus, and to further investigate and identify the causal SNPs that contribute to MIC-1/GDF-15 levels.
KW - Chromosome 19
KW - Community-based individuals
KW - Genome-wide association study
KW - Growth differentiation factor-15
KW - Macrophage inhibitory cytokine-1
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U2 - 10.3389/fgene.2018.00097
DO - 10.3389/fgene.2018.00097
M3 - Article
C2 - 29628937
AN - SCOPUS:85044920475
SN - 1664-8021
VL - 9
JO - Frontiers in Genetics
JF - Frontiers in Genetics
IS - MAR
M1 - 97
ER -