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A meta-analysis of genome-wide association studies of growth differentiation Factor-15 concentration in blood
Journal article   Open access   Peer reviewed

A meta-analysis of genome-wide association studies of growth differentiation Factor-15 concentration in blood

J. Jiang, A. Thalamuthu, J.E. Ho, A. Mahajan, W.E. Ek, D.A. Brown, S.N. Breit, T.J. Wang, U. Gyllensten, M-H Chen, …
Frontiers in Genetics, Vol.9
2018
DOI: https://doi.org/10.3389/fgene.2018.00097
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Abstract

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.

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Collaboration types
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International collaboration
Citation topics
1 Clinical & Life Sciences
1.6 Immunology
1.6.2387 Cytokines and Cancer
Web Of Science research areas
Genetics & Heredity
ESI research areas
Molecular Biology & Genetics
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