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A Meta-Analysis of ...
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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 ...
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2018-03-23
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Frontiers Media S.A.2018
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-354354
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-354354URI
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https://doi.org/10.3389/fgene.2018.00097DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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 ...)
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Thalamuthu, AnbupalamUniv New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia
(author)
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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)
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Mahajan, AnubhaUniv Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
(author)
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Ek, Weronica EUppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab(Swepub:uu)werek336
(author)
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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)
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Breit, Samuel N.St Vincents Hosp, St Vincents Ctr Appl Med Res, Darlinghurst, NSW, Australia
(author)
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Wang, Thomas J.Vanderbilt Univ, Dept Med, Div Cardiol, Nashville, TN USA
(author)
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Gyllensten, Ulf B.Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik(Swepub:uu)ulfgyll
(author)
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Chen, Ming-HueiNHLBI, Populat Sci Branch, NIH, Framingham, MA USA;Framingham Heart Dis Epidemiol Study, Framingham, MA USA
(author)
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Enroth, Stefan,1976-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik(Swepub:uu)stenr451
(author)
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Januzzi, James L., Jr.Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA
(author)
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Lind, LarsUppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)larslind
(author)
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Armstrong, Nicola J.Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Murdoch Univ, Math & Stat, Perth, WA, Australia
(author)
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Kwok, John B.Neurosci Res Australia, Randwick, NSW, Australia;Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia
(author)
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Schofield, Peter R.Neurosci Res Australia, Randwick, NSW, Australia;Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia
(author)
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Wen, WeiUniv New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Prince Wales Hosp, Neuropsychiat Inst, Randwick, NSW, Australia
(author)
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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)
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Johansson, ÅsaUppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik(Swepub:uu)asjoh108
(author)
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Morris, Andrew P.Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England
(author)
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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)
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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)
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Mather, Karen A.Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia
(author)
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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
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In:Frontiers in Genetics: Frontiers Media S.A.91664-8021
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Jiang, Jiyang
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Thalamuthu, Anbu ...
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Ho, Jennifer E.
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Mahajan, Anubha
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Ek, Weronica E
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Brown, David A.
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Breit, Samuel N.
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Wang, Thomas J.
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Gyllensten, Ulf ...
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Lind, Lars
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Armstrong, Nicol ...
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Schofield, Peter ...
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Wen, Wei
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Trollor, Julian ...
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