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Shungin, DmitryUmeå University,Lund University,Lunds universitet,Umeå universitet,Institutionen för odontologi,Medicin,Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States of America,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Lund Univ, Diabet Ctr, Skane Univ Hosp, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden.;Umea Univ, Dept Odontol, Umea, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Unit Med, Umea, Sweden.;MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA.
(författare)
Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions
- Artikel/kapitelEngelska2017
Förlag, utgivningsår, omfång ...
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2017-06-14
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Public Library Science,2017
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:umu-140239
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-140239URI
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https://doi.org/10.1371/journal.pgen.1006812DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:136143634URI
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https://lup.lub.lu.se/record/bd8f70ab-a353-4a59-8cc7-e05a7f65f4ddURI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-330756URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Deng, Wei Q.University of Toronto,Univ Toronto, Dept Stat Sci, Toronto, ON, Canada.
(författare)
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Varga, Tibor V.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Novo Nordisk Foundation Center for Protein Research,Skåne University Hospital,University of Copenhagen,Lund Univ, Diabet Ctr, Skane Univ Hosp, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden.;Univ Copenhagen, Fac Hlth & Med Sci, Translat Dis Syst Biol Grp, Novo Nordisk Fdn Ctr Prot Res, Copenhagen, Denmark.;Lund Univ, Exercise Physiol Grp, Dept Hlth Sci, Lund, Sweden.(Swepub:lu)med-tv_
(författare)
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Luan, Jian'anUniversity of Cambridge,Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England.
(författare)
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Mihailov, EvelinUniversity of Tartu,Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
(författare)
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Metspalu, AndresUniversity of Tartu,Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia.
(författare)
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Morris, Andrew P.University of Tartu,Wellcome Trust Centre for Human Genetics,University of Liverpool,Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
(författare)
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Forouhi, Nita G.University of Cambridge,Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England.
(författare)
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Lindgren, CeciliaBroad Institute,MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
(författare)
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Magnusson, Patrik K. E.Karolinska Institute,Karolinska Institutet,Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
(författare)
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Pedersen, Nancy L.Karolinska Institute,Karolinska Institutet,Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
(författare)
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Hallmans, GöranUmeå University,Umeå universitet,Enheten för biobanksforskning,Umea Univ, Dept Biobank Res, Umea, Sweden.(Swepub:umu)goha0001
(författare)
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Chu, Audrey Y.Harvard Medical School,Harvard Med Sch, Boston, MA USA.
(författare)
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Justice, Anne E.University of North Carolina,Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA.
(författare)
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Graff, MariaelisaUniversity of North Carolina,Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA.
(författare)
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Winkler, Thomas W.University of Regensburg,Univ Regensburg, Dept Genet Epidemiol, Regensburg, DE, Germany.
(författare)
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Rose, Lynda M.Brigham and Women's Hospital / Harvard Medical School,Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
(författare)
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Langenberg, ClaudiaUniversity College London,University of Cambridge,Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England.;UCL, Dept Epidemiol & Publ Hlth, London, England.
(författare)
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Cupples, L. AdrienneBoston University,Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;NHLBI Framingham Heart Study, Framingham, MA USA.
(författare)
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Ridker, Paul M.Harvard Medical School,Brigham and Women's Hospital / Harvard Medical School,Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
(författare)
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Wareham, Nicholas J.University of Cambridge,Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England.
(författare)
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Ong, Ken K.University of Cambridge,Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England.
(författare)
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Loos, Ruth J. F.Icahn School of Medicine at Mount Sinai,Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA.
(författare)
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Chasman, Daniel I.Brigham and Women's Hospital / Harvard Medical School,Harvard Medical School,Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
(författare)
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Ingelsson, Erik,1975-Uppsala universitet,Uppsala University,Stanford University,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.(Swepub:uu)ering425
(författare)
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Kilpeläinen, Tuomas O.University of Copenhagen,Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
(författare)
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Scott, Robert A.University of Cambridge,Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England.
(författare)
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Mägi, ReedikWellcome Trust Centre for Human Genetics,University of Tartu,Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
(författare)
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Paré, GuillaumeMcMaster University,McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada.
(författare)
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Franks, Paul W.Umeå University,Lund University,Lunds universitet,Umeå universitet,Medicin,Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,University of Oxford,Harvard University,Lund Univ, Diabet Ctr, Skane Univ Hosp, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Unit Med, Umea, Sweden.;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Univ Oxford, Radcliff Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.(Swepub:lu)med-plf
(författare)
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Umeå universitetInstitutionen för odontologi
(creator_code:org_t)
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GIANT Consortium
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Ingår i:PLOS Genetics: Public Library Science13:61553-73901553-7404
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Shungin, Dmitry
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Deng, Wei Q.
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Varga, Tibor V.
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Luan, Jian'an
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Mihailov, Evelin
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Metspalu, Andres
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visa fler...
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Morris, Andrew P ...
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Forouhi, Nita G.
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Lindgren, Cecili ...
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Magnusson, Patri ...
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Pedersen, Nancy ...
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Hallmans, Göran
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Chu, Audrey Y.
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Justice, Anne E.
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Graff, Mariaelis ...
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Winkler, Thomas ...
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Rose, Lynda M.
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Langenberg, Clau ...
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Cupples, L. Adri ...
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Ridker, Paul M.
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Wareham, Nichola ...
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Ong, Ken K.
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Loos, Ruth J. F.
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Chasman, Daniel ...
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Ingelsson, Erik, ...
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Kilpeläinen, Tuo ...
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Scott, Robert A.
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Mägi, Reedik
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Paré, Guillaume
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Franks, Paul W.
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