Jiang, Jiyang, Thalamuthu, Anbupalam, Ho, Jennifer E, Mahajan, Anubha, Ek, Weronica E, Brown, David A, Breit, Samuel N, Wang, Thomas J, Gyllensten, Ulf, Chen, Ming-Huei et al (show 13 more authors)
(2018)
A Meta-Analysis of Genome-Wide Association Studies of Growth Differentiation Factor-15 Concentration in Blood.
FRONTIERS IN GENETICS, 9 (MAR).
97-.
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, <i>p</i> = 1.690 × 10<sup>-35</sup>), 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 (<i>p</i> = 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | genome-wide association study, growth differentiation factor-15, macrophage inhibitory cytokine-1, community-based individuals, chromosome 19 |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 02 May 2018 08:09 |
| Last Modified: | 06 Feb 2024 21:44 |
| DOI: | 10.3389/fgene.2018.00097 |
| Open Access URL: | https://www.frontiersin.org/articles/10.3389/fgene... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3020839 |
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