A meta-analysis of genome-wide association studies of growth differentiation factor-15 concentration in blood
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Frontiers Media
2018
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| _version_ | 1797070716994060288 |
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| author | Jiang, J Thalamuthu, A Ho, JE Mahajan, A Ek, WE Brown, DA Breit, SN Wang, TJ Gyllensten, U Chen, M-H Enroth, S Jr, JJL Lind, L Armstrong, NJ Kwok, JB Schofield, PR Wen, W Trollor, JN Johansson, A Morris, AP Vasan, RS Sachdev, PS Mather, KA |
| author_facet | Jiang, J Thalamuthu, A Ho, JE Mahajan, A Ek, WE Brown, DA Breit, SN Wang, TJ Gyllensten, U Chen, M-H Enroth, S Jr, JJL Lind, L Armstrong, NJ Kwok, JB Schofield, PR Wen, W Trollor, JN Johansson, A Morris, AP Vasan, RS Sachdev, PS Mather, KA |
| author_sort | Jiang, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T22:42:57Z |
| format | Journal article |
| id | oxford-uuid:5c374fc7-3545-4b84-98b3-d3e227a74fca |
| institution | University of Oxford |
| last_indexed | 2024-03-06T22:42:57Z |
| publishDate | 2018 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:5c374fc7-3545-4b84-98b3-d3e227a74fca2022-03-26T17:26:50ZA meta-analysis of genome-wide association studies of growth differentiation factor-15 concentration in bloodJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5c374fc7-3545-4b84-98b3-d3e227a74fcaSymplectic Elements at OxfordFrontiers Media2018Jiang, JThalamuthu, AHo, JEMahajan, AEk, WEBrown, DABreit, SNWang, TJGyllensten, UChen, M-HEnroth, SJr, JJLLind, LArmstrong, NJKwok, JBSchofield, PRWen, WTrollor, JNJohansson, AMorris, APVasan, RSSachdev, PSMather, KABlood 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. |
| spellingShingle | Jiang, J Thalamuthu, A Ho, JE Mahajan, A Ek, WE Brown, DA Breit, SN Wang, TJ Gyllensten, U Chen, M-H Enroth, S Jr, JJL Lind, L Armstrong, NJ Kwok, JB Schofield, PR Wen, W Trollor, JN Johansson, A Morris, AP Vasan, RS Sachdev, PS Mather, KA A meta-analysis of genome-wide association studies of growth differentiation factor-15 concentration in blood |
| title | A meta-analysis of genome-wide association studies of growth differentiation factor-15 concentration in blood |
| title_full | A meta-analysis of genome-wide association studies of growth differentiation factor-15 concentration in blood |
| title_fullStr | A meta-analysis of genome-wide association studies of growth differentiation factor-15 concentration in blood |
| title_full_unstemmed | A meta-analysis of genome-wide association studies of growth differentiation factor-15 concentration in blood |
| title_short | A meta-analysis of genome-wide association studies of growth differentiation factor-15 concentration in blood |
| title_sort | meta analysis of genome wide association studies of growth differentiation factor 15 concentration in blood |
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