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  • Jiang, JiyangUniv New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia (author)

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

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-03-23
  • Frontiers Media S.A.2018
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-354354
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-354354URI
  • https://doi.org/10.3389/fgene.2018.00097DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 similar to 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 x 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Thalamuthu, AnbupalamUniv New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia (author)
  • Ho, Jennifer E.Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA (author)
  • Mahajan, AnubhaUniv Oxford, Wellcome Trust Ctr Human Genet, Oxford, England (author)
  • Ek, Weronica EUppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab(Swepub:uu)werek336 (author)
  • Brown, David A.St Vincents Hosp, St Vincents Ctr Appl Med Res, Darlinghurst, NSW, Australia;Westmead Inst Med Res, Inst Clin Pathol & Med Res, Westmead, NSW, Australia;Westmead Hosp, Westmead, NSW, Australia (author)
  • Breit, Samuel N.St Vincents Hosp, St Vincents Ctr Appl Med Res, Darlinghurst, NSW, Australia (author)
  • Wang, Thomas J.Vanderbilt Univ, Dept Med, Div Cardiol, Nashville, TN USA (author)
  • Gyllensten, Ulf B.Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik(Swepub:uu)ulfgyll (author)
  • Chen, Ming-HueiNHLBI, Populat Sci Branch, NIH, Framingham, MA USA;Framingham Heart Dis Epidemiol Study, Framingham, MA USA (author)
  • Enroth, Stefan,1976-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik(Swepub:uu)stenr451 (author)
  • Januzzi, James L., Jr.Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA (author)
  • Lind, LarsUppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)larslind (author)
  • Armstrong, Nicola J.Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Murdoch Univ, Math & Stat, Perth, WA, Australia (author)
  • Kwok, John B.Neurosci Res Australia, Randwick, NSW, Australia;Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia (author)
  • Schofield, Peter R.Neurosci Res Australia, Randwick, NSW, Australia;Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia (author)
  • Wen, WeiUniv New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Prince Wales Hosp, Neuropsychiat Inst, Randwick, NSW, Australia (author)
  • Trollor, Julian N.Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Univ New South Wales, Sch Psychiat, Dept Dev Disabil Neuropsychiat, Sydney, NSW, Australia (author)
  • Johansson, ÅsaUppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik(Swepub:uu)asjoh108 (author)
  • Morris, Andrew P.Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England (author)
  • Vasan, Ramachandran S.Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA;Boston Univ, Sch Med, Dept Med, Epidemiol Sect, Boston, MA 02118 USA;Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA;Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Natl Heart Lung & Blood Inst, Boston, MA USA;Boston Univ, Framingham Heart Study, Boston, MA 02215 USA (author)
  • Sachdev, Perminder S.Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Prince Wales Hosp, Neuropsychiat Inst, Randwick, NSW, Australia (author)
  • Mather, Karen A.Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia (author)
  • Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, AustraliaMassachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA (creator_code:org_t)

Related titles

  • In:Frontiers in Genetics: Frontiers Media S.A.91664-8021

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