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Sökning: onr:"swepub:oai:DiVA.org:uu-354354" > A Meta-Analysis of ...

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

Jiang, Jiyang (författare)
Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia
Thalamuthu, Anbupalam (författare)
Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia
Ho, Jennifer E. (författare)
Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA
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Mahajan, Anubha (författare)
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
Ek, Weronica E (författare)
Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
Brown, David A. (författare)
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
Breit, Samuel N. (författare)
St Vincents Hosp, St Vincents Ctr Appl Med Res, Darlinghurst, NSW, Australia
Wang, Thomas J. (författare)
Vanderbilt Univ, Dept Med, Div Cardiol, Nashville, TN USA
Gyllensten, Ulf B. (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
Chen, Ming-Huei (författare)
NHLBI, Populat Sci Branch, NIH, Framingham, MA USA;Framingham Heart Dis Epidemiol Study, Framingham, MA USA
Enroth, Stefan, 1976- (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
Januzzi, James L., Jr. (författare)
Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA
Lind, Lars (författare)
Uppsala universitet,Kardiovaskulär epidemiologi
Armstrong, Nicola J. (författare)
Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Murdoch Univ, Math & Stat, Perth, WA, Australia
Kwok, John B. (författare)
Neurosci Res Australia, Randwick, NSW, Australia;Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia
Schofield, Peter R. (författare)
Neurosci Res Australia, Randwick, NSW, Australia;Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia
Wen, Wei (författare)
Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Prince Wales Hosp, Neuropsychiat Inst, Randwick, NSW, Australia
Trollor, Julian N. (författare)
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
Johansson, Åsa (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
Morris, Andrew P. (författare)
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England
Vasan, Ramachandran S. (författare)
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
Sachdev, Perminder S. (författare)
Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Prince Wales Hosp, Neuropsychiat Inst, Randwick, NSW, Australia
Mather, Karen A. (författare)
Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia
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 (creator_code:org_t)
2018-03-23
2018
Engelska.
Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 9
Relaterad länk:
https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
https://www.frontier...
https://urn.kb.se/re...
https://doi.org/10.3...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

genome-wide association study
growth differentiation factor-15
macrophage inhibitory cytokine-1
community-based individuals
chromosome 19

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