Academic Journal

A Meta-Analysis of Genome-Wide Association Studies of Growth Differentiation Factor-15 Concentration in Blood

التفاصيل البيبلوغرافية
العنوان: A Meta-Analysis of Genome-Wide Association Studies of Growth Differentiation Factor-15 Concentration in Blood
المؤلفون: Jiyang Jiang, Anbupalam Thalamuthu, Jennifer E. Ho, Anubha Mahajan, Weronica E. Ek, David A. Brown, Samuel N. Breit, Thomas J. Wang, Ulf Gyllensten, Ming-Huei Chen, Stefan Enroth, James L. Januzzi, Lars Lind, Nicola J. Armstrong, John B. Kwok, Peter R. Schofield, Wei Wen, Julian N. Trollor, Åsa Johansson, Andrew P. Morris, Ramachandran S. Vasan, Perminder S. Sachdev, Karen A. Mather
المصدر: Frontiers in Genetics, Vol 9 (2018)
بيانات النشر: Frontiers Media S.A., 2018.
سنة النشر: 2018
المجموعة: LCC:Genetics
مصطلحات موضوعية: genome-wide association study, growth differentiation factor-15, macrophage inhibitory cytokine-1, community-based individuals, chromosome 19, Genetics, QH426-470
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1664-8021
Relation: http://journal.frontiersin.org/article/10.3389/fgene.2018.00097/full; https://doaj.org/toc/1664-8021
DOI: 10.3389/fgene.2018.00097
URL الوصول: https://doaj.org/article/23053b96d5204c01b4adde1b2d257070
رقم الانضمام: edsdoj.23053b96d5204c01b4adde1b2d257070
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:16648021
DOI:10.3389/fgene.2018.00097