Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations

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Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations


نویسنده	o'seaghdha c.m. ,wu h. ,yang q. ,kapur k. ,guessous i. ,zuber a.m. ,köttgen a. ,stoudmann c. ,teumer a. ,kutalik z. ,mangino m. ,dehghan a. ,zhang w. ,eiriksdottir g. ,li g. ,tanaka t. ,portas l. ,lopez l.m. ,hayward c. ,lohman k. ,matsuda k. ,padmanabhan s. ,firsov d. ,sorice r. ,ulivi s. ,brockhaus a.c. ,kleber m.e. ,mahajan a. ,ernst f.d. ,gudnason v. ,launer l.j. ,mace a. ,boerwinckle e. ,arking d.e. ,tanikawa c. ,nakamura y. ,brown m.j. ,gaspoz j.-m. ,theler j.-m. ,siscovick d.s. ,psaty b.m. ,bergmann s. ,vollenweider p. ,vitart v. ,wright a.f. ,zemunik t. ,boban m. ,kolcic i. ,navarro p. ,brown e.m. ,estrada k. ,ding j. ,harris t.b. ,bandinelli s. ,hernandez d. ,singleton a.b. ,girotto g. ,ruggiero d. ,d'adamo a.p. ,robino a. ,meitinger t. ,meisinger c. ,davies g. ,starr j.m. ,chambers j.c. ,boehm b.o. ,winkelmann b.r. ,huang j. ,murgia f. ,wild s.h. ,campbell h. ,morris a.p. ,franco o.h. ,hofman a. ,uitterlinden a.g. ,rivadeneira f. ,völker u. ,hannemann a. ,biffar r. ,hoffmann w. ,shin s.-y. ,lescuyer p. ,henry h. ,schurmann c. ,munroe p.b. ,gasparini p. ,pirastu n. ,ciullo m. ,gieger c. ,märz w. ,lind l. ,spector t.d. ,smith a.v. ,rudan i. ,wilson j.f. ,polasek o. ,deary i.j. ,pirastu m. ,ferrucci l. ,liu y. ,kestenbaum b. ,kooner j.s. ,witteman j.c.m. ,nauck m. ,kao w.h.l. ,wallaschofski h. ,bonny o. ,fox c.s. ,bochud m.
منبع	plos genetics - 2013 - دوره : 9 - شماره : 9
چکیده	Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. apart from casr,the genes associated with serum calcium are largely unknown. we conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤21,679 additional individuals. seven loci (six new regions) in association with serum calcium were identified and replicated. rs1570669 near cyp24a1 (p = 9.1e-12),rs10491003 upstream of gata3 (p = 4.8e-09) and rs7481584 in cars (p = 1.2e-10) implicate regions involved in mendelian calcemic disorders: rs1550532 in dgkd (p = 8.2e-11),also associated with bone density,and rs7336933 near dgkh/kiaa0564 (p = 9.1e-10) are near genes that encode distinct isoforms of diacylglycerol kinase. rs780094 is in gckr. we characterized the expression of these genes in gut,kidney,and bone,and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. our results shed new light on the genetics of calcium homeostasis. © 2013.

آدرس	national heart,lung,and blood institute's framingham heart study,center for population studies,framingham,ma,united states,renal division,massachusetts general hospital,boston,ma, United States, national heart,lung,and blood institute's framingham heart study,center for population studies,framingham,ma,united states,department of biostatistics,boston university,boston,ma,united states,department of medical biology,university of split,school of medicine,split, Croatia, national heart,lung,and blood institute's framingham heart study,center for population studies,framingham,ma,united states,department of biostatistics,boston university,boston,ma, United States, department of medical genetics,university of lausanne,lausanne, Switzerland, institute of social and preventive medicine (iumsp),lausanne university hospital,lausanne,switzerland,unit of population epidemiology,division of primary care medicine,department of community medicine and primary care and emergency medicine,geneva university hospitals,geneva,switzerland,geriatric unit,azienda sanitaria firenze (asf),florence, Italy, department of pharmacology and toxicology,university of lausanne,lausanne, Switzerland, renal division,freiburg university hospital,freiburg,germany,department of epidemiology,johns hopkins bloomberg school of public health,baltimore,md, United States, department of pharmacology and toxicology,university of lausanne,lausanne, Switzerland, interfaculty institute for genetics and functional genomics,ernst-moritz-arndt-university greifswald,greifswald, Germany, department of medical genetics,university of lausanne,lausanne,switzerland,swiss institute of bioinformatics,lausanne, Switzerland, king's college london,st. thomas' hospital campus,london, United Kingdom, department of epidemiology,erasmus medical center,rotterdam, Netherlands, catheter lab,cardiology,ealing hospital,southall,middlesex,united kingdom,department of epidemiology and biostatistics,school of public health,imperial college london,london, United Kingdom, icelandic heart association research institute,kopavogur, Iceland, cardiovascular health research unit,university of washington,seattle,wa, United States, clinical research branch,national institute on aging,baltimore,md, United States, institute of population genetics,cnr-traversa la crucca,reg. baldinca li punti,sassari, Italy, centre for cognitive ageing and cognitive epidemiology,the university of edinburgh,edinburgh, United Kingdom, mrc human genetics unit,mrc igmm,university of edinburgh,edinburgh, United Kingdom, cardiology group,clinphenomics gmbhandco kg,frankfurt-sachsenhausen, Germany, laboratory of molecular medicine,human genome center,institute of medical science,university of tokyo,tokyo, Japan, bhf glasgow cardiovascular research centre,division of cardiovascular and medical sciences,university of glasgow,glasgow, United Kingdom, department of pharmacology and toxicology,university of lausanne,lausanne, Switzerland, institute of genetics and biophysics 'adriano-buzzati traverso',cnr,napoli, Italy, institute for maternal and child health - irccs burlo garofolo,trieste, Italy, institute of genetic epidemiology,helmholtz zentrum münchen - german research center for environmental health,neuherberg,germany,department of medicine i,university hospital grosshadern,ludwig-maximilians university munich,munich, Germany, department of internal medicine ii - cardiology,university of ulm medical centre,ulm,germany,mannheim institute of public health,social and preventive medicine,university of heidelberg,mannheim, Germany, wellcome trust centre for human genetics,roosevelt drive,oxford, United Kingdom, interfaculty institute for genetics and functional genomics,ernst-moritz-arndt-university greifswald,greifswald, Germany, icelandic heart association research institute,kopavogur,iceland,university of iceland,reykjavik, Iceland, laboratory of epidemiology,demography and biometry,national institute on aging,bethesda,md, United States, department of medical genetics,university of lausanne,lausanne,switzerland,swiss institute of bioinformatics,lausanne, Switzerland, university of texas health science center at houston,houston,tx, United States, mckusick-nathans institute of genetic medicine,johns hopkins university school of medicine,baltimore,md, United States, laboratory of molecular medicine,human genome center,institute of medical science,university of tokyo,tokyo, Japan, laboratory of molecular medicine,human genome center,institute of medical science,university of tokyo,tokyo, Japan, cambridge institute of medical research,university of cambridge,cambridge, United Kingdom, department of internal medicine,erasmus medical center,rotterdam, Netherlands, unit of population epidemiology,division of primary care medicine,department of community medicine and primary care and emergency medicine,geneva university hospitals,geneva, Switzerland, cardiovascular health research unit,university of washington,seattle,wa,united states,departments of medicine and epidemiology,university of washington,seattle,wa, United States, cardiovascular health research unit,university of washington,seattle,wa,united states,group health research institute,group health cooperative,seattle,wa,united states,departments of medicine,epidemiology and health services,university of washington,seattle,wa, United States, department of medical genetics,university of lausanne,lausanne,switzerland,swiss institute of bioinformatics,lausanne, Switzerland, department of medicine,internal medicine,lausanne university hospital,lausanne, Switzerland, mrc human genetics unit,mrc igmm,university of edinburgh,edinburgh, United Kingdom, mrc human genetics unit,mrc igmm,university of edinburgh,edinburgh, United Kingdom, university of split,split, Croatia, department of pharmacology,university of split,split, Croatia, university of split,split, Croatia, mrc human genetics unit,mrc igmm,university of edinburgh,edinburgh, United Kingdom, division of laboratory medicine,geneva university hospitals,geneva, Switzerland, department of internal medicine,wake forest school of medicine,winston-salem,nc, United States, division of laboratory medicine,geneva university hospitals,geneva, Switzerland, laboratory of epidemiology,demography and biometry,national institute on aging,bethesda,md, United States, department of human genetics,wellcome trust sanger institute,hinxton,cambridge, United Kingdom, molecular genetics section,laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, molecular genetics section,laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, institute for maternal and child health - irccs burlo garofolo,trieste, Italy, institute of genetics and biophysics 'adriano-buzzati traverso',cnr,napoli, Italy, institute for maternal and child health - irccs burlo garofolo,trieste, Italy, institute for maternal and child health - irccs burlo garofolo,trieste, Italy, institute of human genetics,helmholtz zentrum münchen - german research center for environmental health,neuherberg,germany,department of computer science and networking,wentworth institute of technology,boston,ma, United States, institute of epidemiology ii,helmholtz zentrum münchen - german research center for environmental health,neuherberg, Germany, centre for cognitive ageing and cognitive epidemiology,the university of edinburgh,edinburgh, United Kingdom, centre for cognitive ageing and cognitive epidemiology,the university of edinburgh,edinburgh, United Kingdom, catheter lab,cardiology,ealing hospital,southall,middlesex,united kingdom,department of epidemiology and biostatistics,school of public health,imperial college london,london,united kingdom,epidemiology and biostatistics,imperial college london,norfolk place,london, United Kingdom, ulm university medical centre,department of internal medicine i,ulm university,ulm,germany,lkc school of medicine,imperial college london and nanyang technological university,singapore, Singapore, department of epidemiology,rollins school of public health,emory university,atlanta,ga, United States, division of primary care medicine,department of community medicine and primary care and emergency medicine,geneva university hospitals,geneva, Switzerland, institute of population genetics,cnr-traversa la crucca,reg. baldinca li punti,sassari, Italy, centre for population health sciences,the university of edinburgh medical school,edinburgh, United Kingdom, centre for population health sciences,the university of edinburgh medical school,edinburgh, United Kingdom, wellcome trust centre for human genetics,roosevelt drive,oxford, United Kingdom, department of epidemiology,erasmus medical center,rotterdam, Netherlands, department of epidemiology,erasmus medical center,rotterdam, Netherlands, department of internal medicine,wake forest school of medicine,winston-salem,nc, United States, department of internal medicine,wake forest school of medicine,winston-salem,nc, United States, interfaculty institute for genetics and functional genomics,ernst-moritz-arndt-university greifswald,greifswald, Germany, institute of clinical chemistry and laboratory medicine,university medicine greifswald,ernst-moritz-arndt university greifswald,greifswald, Germany, department of prosthetic dentistry,gerostomatology and dental materials,university medicine greifswald,greifswald, Germany, institute for community medicine,university medicine greifswald,greifswald, Germany, human genetics,wellcome trust sanger institute,hinxton, United Kingdom, department of biostatistical sciences,division of public health sciences,wake forest school of medicine,winston-salem,nc, United States, clinical chemistry laboratory,lausanne university hospital,lausanne, Switzerland, interfaculty institute for genetics and functional genomics,ernst-moritz-arndt-university greifswald,greifswald, Germany, william harvey research institute,barts and the london school of medicine and dentistry,queen mary university of london,london, United Kingdom, institute for maternal and child health - irccs burlo garofolo,trieste, Italy, institute for maternal and child health - irccs burlo garofolo,trieste, Italy, institute of genetics and biophysics 'adriano-buzzati traverso',cnr,napoli, Italy, institute of genetic epidemiology,helmholtz zentrum münchen - german research center for environmental health,neuherberg, Germany, mannheim institute of public health,social and preventive medicine,university of heidelberg,mannheim,germany,synlab centre of laboratory diagnostics,heidelberg, Germany, institute of medical sciences,uppsala university hospital,uppsala, Sweden, king's college london,st. thomas' hospital campus,london, United Kingdom, icelandic heart association research institute,kopavogur,iceland,university of iceland,reykjavik, Iceland, centre for population health sciences,the university of edinburgh medical school,edinburgh, United Kingdom, centre for population health sciences,the university of edinburgh medical school,edinburgh, United Kingdom, university of split,split, Croatia, centre for cognitive ageing and cognitive epidemiology,the university of edinburgh,edinburgh, United Kingdom, institute of population genetics,cnr-traversa la crucca,reg. baldinca li punti,sassari, Italy, laboratory of epidemiology,demography and biometry,national institute on aging,bethesda,md, United States, department of epidemiology and prevention,division of public health sciences,wake forest school of medicine,winston-salem,nc, United States, department of medicine,division of nephrology,university of washington,seattle,wa, United States, catheter lab,cardiology,ealing hospital,southall,middlesex,united kingdom,national heart and lung institute,cardiovascular science,hammersmith hospital,hammersmith campus,imperial college london,london,united kingdom,imperial college healthcare nhs trust,london, United Kingdom, department of epidemiology,erasmus medical center,rotterdam, Netherlands, institute of clinical chemistry and laboratory medicine,university medicine greifswald,ernst-moritz-arndt university greifswald,greifswald, Germany, department of epidemiology,johns hopkins bloomberg school of public health,baltimore,md,united states,welch center for prevention,epidemiology and clinical research,john hopkins university,baltimore,md, United States, institute of clinical chemistry and laboratory medicine,university medicine greifswald,ernst-moritz-arndt university greifswald,greifswald, Germany, department of pharmacology and toxicology,university of lausanne,lausanne,switzerland,service of nephrology,lausanne university hospital,lausanne, Switzerland, national heart,lung,and blood institute's framingham heart study,center for population studies,framingham,ma,united states,division of endocrinology,brigham and women's hospital and harvard medical school,boston,ma, United States, institute of social and preventive medicine (iumsp),lausanne university hospital,lausanne, Switzerland



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