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Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms
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نویسنده
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zhai g. ,teumer a. ,stolk l. ,perry j.r.b. ,vandenput l. ,coviello a.d. ,koster a. ,bell j.t. ,bhasin s. ,eriksson j. ,eriksson a. ,ernst f. ,ferrucci l. ,frayling t.m. ,glass d. ,grundberg e. ,haring r. ,hedmanå a.k. ,hofman a. ,kiel d.p. ,kroemer h.k. ,liu y. ,lunetta k.l. ,maggio m. ,lorentzon m. ,mangino m. ,melzer d. ,miljkovic i. ,nica a. ,penninx b.w.j.h. ,vasan r.s. ,rivadeneira f. ,small k.s. ,soranzo n. ,uitterlinden a.g. ,völzke h. ,wilson s.g. ,xi l. ,zhuang w.v. ,harris t.b. ,murabito j.m. ,ohlsson c. ,murray a. ,de jong f.h. ,spector t.d. ,wallaschofski h.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 4
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چکیده
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Dehydroepiandrosterone sulphate (dheas) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. its serum concentration declines significantly with increasing age,which has led to speculation that a relative dheas deficiency may contribute to the development of common age-related diseases or diminished longevity. we conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common snps associated with serum dheas concentrations. genes at or near the identified loci include zkscan5 (rs11761528; p = 3.15×10-36),sult2a1 (rs2637125; p = 2.61×10-19),arpc1a (rs740160; p = 1.56×10-16),trim4 (rs17277546; p = 4.50×10-11),bmf (rs7181230; p = 5.44×10-11),hhex (rs2497306; p = 4.64×10-9),bcl2l11 (rs6738028; p = 1.72×10-8),and cyp2c9 (rs2185570; p = 2.29×10-8). these genes are associated with type 2 diabetes,lymphoma,actin filament assembly,drug and xenobiotic metabolism,and zinc finger proteins. several snps were associated with changes in gene expression levels,and the related genes are connected to biological pathways linking dheas with ageing. this study provides much needed insight into the function of dheas.
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آدرس
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department of twin research and genetic epidemiology,king's college london,london, United Kingdom, interfaculty institute for genetics and functional genomics,university of greifswald,greifswald, Germany, department of internal medicine,erasmus mc rotterdam,rotterdam,netherlands,netherlands consortium of healthy ageing,rotterdam, Netherlands, genetics of complex traits,peninsula medical school,university of exeter,exeter,united kingdom,wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, sections of general internal medicine,preventive medicine,cardiology and endocrinology,diabetes and nutrition,department of medicine,boston university school of medicine,boston,ma, United States, laboratory for epidemiology,demography,and biometry,national institute on aging,bethesda,md, United States, department of twin research and genetic epidemiology,king's college london,london,united kingdom,wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, section of endocrinology,diabetes,and nutrition,claude d. pepper older americans independence center,boston university school of medicine,boston,ma, United States, department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, interfaculty institute for genetics and functional genomics,university of greifswald,greifswald, Germany, clinical research branch,national institute on aging,baltimore,md, United States, genetics of complex traits,peninsula medical school,university of exeter,exeter, United Kingdom, department of twin research and genetic epidemiology,king's college london,london, United Kingdom, department of twin research and genetic epidemiology,king's college london,london,united kingdom,wellcome trust sanger institute,hixton, United Kingdom, institute for clinical chemistry and laboratory medicine,university of greifswald,greifswald, Germany, wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, netherlands consortium of healthy ageing,rotterdam,netherlands,department of epidemiology,erasmus mc,rotterdam, Netherlands, hebrew senior life institute for aging research and harvard medical school,boston,ma, United States, center of pharmacology and experimental therapeutics,department of pharmacology,university of greifswald,greifswald, Germany, department of epidemiology and prevention,wake forest university health sciences,winston-salem,nc, United States, department of biostatistics,boston university school of public health,boston,ma, United States, department of internal medicine and biomedical sciences,section of geriatrics,university of parma,parma, Italy, department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, department of twin research and genetic epidemiology,king's college london,london, United Kingdom, genetics of complex traits,peninsula medical school,university of exeter,exeter, United Kingdom, department of epidemiology,university of pittsburgh,pittsburg,pa, United States, wellcome trust sanger institute,hixton,united kingdom,department of genetic medicine and development,university of geneva medical school,geneva, Switzerland, department of psychiatry,vu university medical center,amsterdam, Netherlands, sections of general internal medicine,preventive medicine,cardiology and endocrinology,diabetes and nutrition,department of medicine,boston university school of medicine,boston,ma,united states,the national heart lung and blood institute's framingham heart study,framingham,ma, United States, department of internal medicine,erasmus mc rotterdam,rotterdam,netherlands,netherlands consortium of healthy ageing,rotterdam, Netherlands, department of twin research and genetic epidemiology,king's college london,london,united kingdom,wellcome trust sanger institute,hixton, United Kingdom, department of twin research and genetic epidemiology,king's college london,london,united kingdom,wellcome trust sanger institute,hixton, United Kingdom, department of internal medicine,erasmus mc rotterdam,rotterdam,netherlands,netherlands consortium of healthy ageing,rotterdam,netherlands,department of epidemiology,erasmus mc,rotterdam, Netherlands, institute for community medicine,university of greifswald,greifswald, Germany, department of twin research and genetic epidemiology,king's college london,london,united kingdom,department of endocrinology and diabetes,sir charles gairdner hospital,nedlands,australia,school of medicine and pharmacology,university of western australia,nedlands, Australia, molecular medicine - computational biology,pfizer worldwide r and d,groton,ct, United States, department of biostatistics,boston university school of public health,boston,ma, United States, laboratory for epidemiology,demography,and biometry,national institute on aging,bethesda,md, United States, sections of general internal medicine,preventive medicine,cardiology and endocrinology,diabetes and nutrition,department of medicine,boston university school of medicine,boston,ma,united states,the national heart lung and blood institute's framingham heart study,framingham,ma, United States, department of internal medicine,institute of medicine,sahlgrenska academy,university of gothenburg,gothenburg, Sweden, genetics of complex traits,peninsula medical school,university of exeter,exeter, United Kingdom, department of internal medicine,erasmus mc rotterdam,rotterdam, Netherlands, department of twin research and genetic epidemiology,king's college london,london, United Kingdom, institute for clinical chemistry and laboratory medicine,university of greifswald,greifswald, Germany
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