|
|
|
|
A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol
|
|
|
|
|
|
|
|
نویسنده
|
surakka i. ,isaacs a. ,karssen l.c. ,laurila p.-p.p. ,middelberg r.p.s. ,tikkanen e. ,ried j.s. ,lamina c. ,mangino m. ,igl w. ,hottenga j.-j. ,lagou v. ,van der harst p. ,leach i. ,esko t. ,kutalik z. ,wainwright n.w. ,struchalin m.v. ,sarin a.-p. ,kangas a.j. ,viikari j.s. ,perola m. ,rantanen t. ,petersen a.-k. ,soininen p. ,johansson å. ,soranzo n. ,heath a.c. ,papamarkou t. ,prokopenko i. ,tönjes a. ,kronenberg f. ,döring a. ,rivadeneira f. ,montgomery g.w. ,whitfield j.b. ,kähönen m. ,lehtimäki t. ,freimer n.b. ,willemsen g. ,de geus e.j.c. ,palotie a. ,sandhu m.s. ,waterworth d.m. ,metspalu a. ,stumvoll m. ,uitterlinden a.g. ,jula a. ,navis g. ,wijmenga c. ,wolffenbuttel b.h.r. ,taskinen m.-r. ,ala-korpela m. ,kaprio j. ,kyvik k.o. ,boomsma d.i. ,pedersen n.l. ,gyllensten u. ,wilson j.f. ,rudan i. ,campbell h. ,pramstaller p.p. ,spector t.d. ,witteman j.c.m. ,eriksson j.g. ,salomaa v. ,oostra b.a. ,raitakari o.t. ,wichmann h.-e. ,gieger c. ,järvelin m.-r. ,martin n.g. ,hofman a. ,mccarthy m.i. ,peltonen l. ,van duijn c.m. ,aulchenko y.s. ,ripatti s.
|
|
منبع
|
plos genetics - 2011 - دوره : 7 - شماره : 10
|
|
چکیده
|
Recent genome-wide association (gwa) studies described 95 loci controlling serum lipid levels. these common variants explain ~25% of the heritability of the phenotypes. to date,no unbiased screen for gene-environment interactions for circulating lipids has been reported. we screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (gwa) data from 18 population-based cohorts with european ancestry (maximum n = 32,225). we collected 8 further cohorts (n = 17,102) for replication,and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (whr) on total cholesterol (tc) with a combined p-value of 4.79×10 -9. there were two potential candidate genes in the region,pcdh7 and cckar,with differential expression levels for rs6448771 genotypes in adipose tissue. the effect of whr on tc was strongest for individuals carrying two copies of g allele,for whom a one standard deviation (sd) difference in whr corresponds to 0.19 sd difference in tc concentration,while for a allele homozygous the difference was 0.12 sd. our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. however,more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus. © 2011 surakka et al.
|
|
|
|
|
آدرس
|
institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,public health genomics unit,national institute for health and welfare,helsinki, Finland, genetic epidemiology unit,department of epidemiology,erasmus university medical center,rotterdam,netherlands,centre for medical systems biology,netherlands genomics initiative,leiden, Netherlands, genetic epidemiology unit,department of epidemiology,erasmus university medical center,rotterdam, Netherlands, institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,public health genomics unit,national institute for health and welfare,helsinki,finland,department of medical genetics,haartman institute,university of helsinki,helsinki university central hospital,helsinki, Finland, queensland institute of medical research,brisbane,australia,department of medicine,prince charles hospital,chermside, Australia, institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,public health genomics unit,national institute for health and welfare,helsinki, Finland, institute of genetic epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, division of genetic epidemiology,department of medical genetics,molecular and clinical pharmacology,innsbruck medical university,innsbruck, Austria, department of twin research and genetic epidemiology,king's college london,london, United Kingdom, department of immunology,genetics,and pathology,university of uppsala,uppsala, Sweden, department of biological psychology,vu university amsterdam,amsterdam, Netherlands, oxford centre for diabetes,endocrinology,and metabolism,university of oxford,oxford,united kingdom,wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, department of cardiology,university medical center groningen,university of groningen,groningen, Netherlands, department of cardiology,university medical center groningen,university of groningen,groningen, Netherlands, the estonian genome center,center of translational genomics of the university of tartu,tartu,estonia,the institute of molecular and cellular biology,university of tartu,tartu, Estonia, department of medical genetics,university of lausanne,lausanne,switzerland,swiss institute of bioinformatics,lausanne, Switzerland, genetic epidemiology group,wellcome trust sanger institute,hinxton,united kingdom,non-communicable disease research group,department of public health and primary care,university of cambridge,cambridge, United Kingdom, genetic epidemiology unit,department of epidemiology,erasmus university medical center,rotterdam, Netherlands, institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,public health genomics unit,national institute for health and welfare,helsinki, Finland, computational medicine research group,institute of clinical medicine,university of oulu and biocenter oulu,oulu, Finland, department of medicine,university of turku and turku university hospital,turku, Finland, institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,public health genomics unit,national institute for health and welfare,helsinki,finland,the estonian genome center,center of translational genomics of the university of tartu,tartu, Estonia, department of health sciences,gerontology research centre,university of jyväskylä,jyväskylä, Finland, institute of genetic epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, nmr metabonomics laboratory,department of biosciences,university of eastern finland,kuopio, Finland, department of immunology,genetics,and pathology,university of uppsala,uppsala, Sweden, department of twin research and genetic epidemiology,king's college london,london,united kingdom,genetic epidemiology group,wellcome trust sanger institute,hinxton, United Kingdom, department of psychiatry,washington university school of medicine,st. louis,mo, United States, genetic epidemiology group,wellcome trust sanger institute,hinxton,united kingdom,non-communicable disease research group,department of public health and primary care,university of cambridge,cambridge, United Kingdom, oxford centre for diabetes,endocrinology,and metabolism,university of oxford,oxford,united kingdom,wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, medical department,university of leipzig,leipzig,germany,ifb adipositydiseases,university of leipzig,leipzig, Germany, division of genetic epidemiology,department of medical genetics,molecular and clinical pharmacology,innsbruck medical university,innsbruck, Austria, institute of epidemiology i,helmholtz zentrum münchen,german research center for environmental health,neuherberg,germany,institute of epidemiology ii,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, department of epidemiology,erasmus mc,rotterdam,netherlands,department of internal medicine,erasmus mc,rotterdam,netherlands,netherlands genomics initiative (ngi)-sponsored netherlands consortium for healthy aging (ncha),leiden, Netherlands, queensland institute of medical research,brisbane, Australia, queensland institute of medical research,brisbane, Australia, department of clinical physiology,tampere university hospital,tampere,finland,medical school,university of tampere,tampere, Finland, medical school,university of tampere,tampere,finland,department of clinical chemistry,tampere university hospital,tampere, Finland, department of psychiatry,university of california los angeles,los angeles,united states,center for neurobehavioral genetics,semel institute for neuroscience and human behavior,university of california los angeles,los angeles, United States, department of biological psychology,vu university amsterdam,amsterdam, Netherlands, department of biological psychology,vu university amsterdam,amsterdam, Netherlands, institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,department of medical genetics,haartman institute,university of helsinki,helsinki university central hospital,helsinki,finland,genetic epidemiology group,wellcome trust sanger institute,hinxton,united kingdom,the broad institute of massachusetts institute of technology,harvard university,cambridge,ma, United States, genetic epidemiology group,wellcome trust sanger institute,hinxton,united kingdom,non-communicable disease research group,department of public health and primary care,university of cambridge,cambridge, United Kingdom, genetics,medicines discovery,and development,glaxosmithkline,philadelphia,pa, United States, the estonian genome center,center of translational genomics of the university of tartu,tartu,estonia,the institute of molecular and cellular biology,university of tartu,tartu,estonia,the estonian biocentre,tartu, Estonia, department of medicine,university of leipzig,leipzig, Germany, department of epidemiology,erasmus mc,rotterdam,netherlands,department of internal medicine,erasmus mc,rotterdam,netherlands,netherlands genomics initiative (ngi)-sponsored netherlands consortium for healthy aging (ncha),leiden, Netherlands, department of chronic disease prevention,national institute for health and welfare,turku, Finland, division of nephrology,department of internal medicine,university medical center groningen,university of groningen,groningen, Netherlands, department of genetics,university medical centre groningen,university of groningen,groningen, Netherlands, department of endocrinology,university medical center groningen,university of groningen,groningen, Netherlands, department of medicine,helsinki university central hospital,helsinki, Finland, computational medicine research group,institute of clinical medicine,university of oulu and biocenter oulu,oulu,finland,nmr metabonomics laboratory,department of biosciences,university of eastern finland,kuopio,finland,department of internal medicine and biocenter oulu,clinical research center,university of oulu,oulu, Finland, institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,department of public health,university of helsinki,helsinki,finland,unit for child and adolescent mental health,national institute for health and welfare,helsinki, Finland, institute of regional health services research,university of southern denmark,odense,denmark,odense patient data explorative network (open),odense university hospital,odense, Denmark, department of biological psychology,vu university amsterdam,amsterdam, Netherlands, department of medical epidemiology and biostatistics,karolinska institutet,stockholm, Sweden, department of immunology,genetics,and pathology,university of uppsala,uppsala, Sweden, centre for population health sciences,university of edinburgh medical school,edinburgh, United Kingdom, centre for population health sciences,university of edinburgh medical school,edinburgh,united kingdom,croatian centre for global health,university of split medical school,split, Croatia, centre for population health sciences,university of edinburgh medical school,edinburgh, United Kingdom, institute of genetic medicine,european academy bozen/bolzano (eurac),bolzano,italy,affiliated institute of the university of lübeck,lübeck,germany,department of neurology,university of lübeck,lübeck,germany,department of neurology,central hospital of bolzano,bolzano, Italy, department of twin research and genetic epidemiology,king's college london,london, United Kingdom, department of epidemiology,erasmus mc,rotterdam,netherlands,department of internal medicine,erasmus mc,rotterdam,netherlands,netherlands genomics initiative (ngi)-sponsored netherlands consortium for healthy aging (ncha),leiden, Netherlands, department of general practice and primary health care,university of helsinki,helsinki,finland,unit of general practice,helsinki university central hospital,helsinki,finland,folkhälsan research centre,helsinki,finland,vasa central hospital,vasa,finland,department of health promotion and chronic disease prevention,national institute for health and welfare,helsinki, Finland, unit of chronic disease epidemiology and prevention,national institute for health and welfare,helsinki, Finland, department of clinical genetics,erasmus mc,rotterdam, Netherlands, research centre of applied and preventive cardiovascular medicine,university of turku,turku,finland,clinical physiology,university of turku and turku university hospital,turku, Finland, institute of epidemiology i,helmholtz zentrum münchen,german research center for environmental health,neuherberg,germany,institute of medical informatics,biometry and epidemiology,chair of epidemiology,ludwig-maximilians-universität,munich,germany,klinikum grosshadern,munich, Germany, institute of genetic epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, department of epidemiology and biostatistics,school of public health,imperial college london,london, Germany, queensland institute of medical research,brisbane, Australia, department of epidemiology,erasmus mc,rotterdam,netherlands,department of internal medicine,erasmus mc,rotterdam,netherlands,netherlands genomics initiative (ngi)-sponsored netherlands consortium for healthy aging (ncha),leiden, Netherlands, oxford centre for diabetes,endocrinology,and metabolism,university of oxford,oxford,united kingdom,wellcome trust centre for human genetics,university of oxford,oxford,united kingdom,oxford nihr biomedical research centre,churchill hospital,oxford, Germany, institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,public health genomics unit,national institute for health and welfare,helsinki,finland,department of medical genetics,haartman institute,university of helsinki,helsinki university central hospital,helsinki,finland,department of medical genetics,university of lausanne,lausanne,switzerland,the broad institute of massachusetts institute of technology,harvard university,cambridge,ma, United States, genetic epidemiology unit,department of epidemiology,erasmus university medical center,rotterdam,netherlands,centre for medical systems biology,netherlands genomics initiative,leiden,netherlands,netherlands genomics initiative (ngi)-sponsored netherlands consortium for healthy aging (ncha),leiden, Netherlands, genetic epidemiology unit,department of epidemiology,erasmus university medical center,rotterdam, Netherlands, institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,public health genomics unit,national institute for health and welfare,helsinki,finland,genetic epidemiology group,wellcome trust sanger institute,hinxton, United Kingdom
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|