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Shared genetic risk factors of intracranial,abdominal,and thoracic aneurysms
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نویسنده
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van't hof f.n.g. ,ruigrok y.m. ,lee c.h. ,ripke s. ,anderson g. ,de andrade m. ,baas a.f. ,blankensteijn j.d. ,böttinger e.p. ,bown m.j. ,broderick j. ,bijlenga p. ,carrell d.s. ,crawford d.c. ,crosslin d.r. ,ebeling c. ,eriksson j.g. ,fornage m. ,foroud t. ,von und zu fraunberg m. ,friedrich c.m. ,gaál e.i. ,gottesman o. ,guo d.-c. ,harrison s.c. ,hernesniemi j. ,hofman a. ,inoue i. ,jääskeläinen j.e. ,jones g.t. ,kiemeney l.a.l.m. ,kivisaari r. ,ko n. ,koskinen s. ,kubo m. ,kullo i.j. ,kuivaniemi h. ,kurki m.i. ,laakso a. ,lai d. ,leal s.m. ,lehto h. ,lemaire s.a. ,low s.-k. ,malinowski j. ,mccarty c.a. ,milewicz d.m. ,mosley t.h. ,nakamura y. ,nakaoka h. ,niemelä m. ,pacheco j. ,peissig p.l. ,pera j. ,rasmussen-torvik l. ,ritchie m.d. ,rivadeneira f. ,van rij a.m. ,santos-cortez r.p. ,saratzis a. ,slowik a. ,takahashi a. ,tromp g. ,uitterlinden a.g. ,verma s.s. ,vermeulen s.h. ,wang g.t. ,han b. ,rinkel g.j.e. ,de bakker p.i.w. ,verissimo a. ,wright b.j. ,bumpstead s. ,gretarsdottir s. ,badger s.a. ,child a.h. ,clough r.e. ,cockerill g. ,hafez h. ,scott d.j.a. ,futers s. ,sohrabi s. ,smith a. ,thompson m.m. ,van bockxmeer f.m. ,matthiasson s.e. ,thorleifsson g. ,thorsteinsdottir u. ,teijink j.a.w. ,wijmenga c. ,de graaf j. ,kiemeney l.a. ,palmen j. ,smith a.j. ,lindholt j.s. ,bradley d.t. ,waltham m. ,edkins s. ,gwilliam r. ,hunt s.e. ,potter s. ,golledge j. ,eriksson p. ,norman p.e. ,powell j.t. ,stefansson k. ,thompson j.r. ,humphries s.e. ,sayers r.d. ,deloukas p. ,samani n.j. ,phillip l.v. ,hill g.b. ,williams m.j.a. ,thomson i.a. ,krysa j. ,wilkins g.t. ,merriman t.r. ,vasudevan t.m. ,lewis d.r. ,blair r.d. ,hill a.a.
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منبع
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journal of the american heart association - 2016 - دوره : 5 - شماره : 7
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چکیده
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Background--intracranial aneurysms (ias),abdominal aortic aneurysms (aaas),and thoracic aortic aneurysms (taas) all have a familial predisposition. given that aneurysm types are known to co-occur,we hypothesized that there may be shared genetic risk factors for ias,aaas,and taas. methods and results--we performed a mega-analysis of 1000 genomes project-imputed genome-wide association study (gwas) data of 4 previously published aneurysm cohorts: 2 ia cohorts (in total 1516 cases,4305 controls),1 aaa cohort (818 cases,3004 controls),and 1 taa cohort (760 cases,2212 controls),and observed associations of 4 known ia,aaa,and/or taa risk loci (9p21,18q11,15q21,and 2q33) with consistent effect directions in all 4 cohorts. we calculated polygenic scores based on ia-,aaa-,and taa-associated snps and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. similarly,linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. last,we evaluated the evidence for 14 previously published aneurysm risk singlenucleotide polymorphisms through collaboration in extended aneurysm cohorts,with a total of 6548 cases and 16 843 controls (ia) and 4391 cases and 37 904 controls (aaa),and found nominally significant associations for ia risk locus 18q11 near rbbp8 to aaa (odds ratio [or]=1.11; p=4.1910-5) and for taa risk locus 15q21 near fbn1 to aaa (or=1.07; p=1.1910-3). conclusions--although there was no evidence for polygenic overlap between ias,aaas,and taas,we found nominally significant effects of two established risk loci for ias and taas in aaas. these two loci will require further replication. © 2016 the authors.
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کلیدواژه
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Abdominal aortic aneurysm; Genome wide association study; Intracranial aneurysm; Thoracic aortic aneurysm
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آدرس
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utrecht stroke center,department of neurology and neurosurgery,rudolf magnus institute of neuroscience, Netherlands, utrecht stroke center,department of neurology and neurosurgery,rudolf magnus institute of neuroscience, Netherlands, department of convergence medicine,university of ulsan college of medicine and asan institute for life sciences,asan medical center,seoul, South Korea, university medical center utrecht,utrecht,netherlands,department of psychiatry and psychotherapy,charité,universitätsmedizin berlin,berlin,germany,division of human genetics,national institute of genetics,mishima, Japan, the george institute for international health,university of sydney, Australia, mayo clinic,rochester,ny, United States, department of medical genetics,center for molecular medicine, Netherlands, department of vascular surgery,vu medical center,amsterdam, Netherlands, icahn school of medicine mount sinai,the charles bronfman institute for personalized medicine,new york,ny, United States, department of cardiovascular sciences,nihr leicester cardiovascular biomedical research unit,university of leicester, United Kingdom, department of neurology,jagiellonian university,krakow,poland,department of biomedical sciences,stellenbosch university,tygerberg, South Africa, center for human genetics,marshfield clinic research foundation,marshfield,wi, United States, group health research institute,seattle,wa, United States, department of epidemiology and biostatistics,institute for computational biology,case western reserve university,cleveland,oh,united states,center for human genetics research,vanderbilt university,nashville,tn, United States, division of medical genetics,department of medicine,university of washington,seattle,wa, United States, fraunhofer institut algorithmen und wissenschaftliches rechnen,sankt augustin, Germany, department of chronic disease prevention,national institute for health and welfare,helsinki,finland,folkhälsan research center,helsinki,finland,department of general practice and primary health care,helsinki university hospital,university of helsinki, Finland, human genetics center and institute of molecular medicine,university of texas health science center,houston,tx, United States, department of medical and molecular genetics,indiana university school of medicine,indianapolis,in, United States, neurosurgery of neurocenter,kuopio university hospital,kuopio, Finland, department of computer science,university of applied science and arts,dortmund, Germany, institute for molecular medicine finland (fimm),university of helsinki,finland,public health genomics unit,department of chronic disease prevention,national institute for health and welfare,helsinki,finland,department of neurosurgery,helsinki university central hospital,helsinki, Finland, icahn school of medicine mount sinai,the charles bronfman institute for personalized medicine,new york,ny, United States, center for integrative medical sciences,riken,kanagawa, Japan, department of cardiovascular science,university of leicester, United Kingdom, department of neurosurgery,helsinki university central hospital,helsinki, Finland, departments of epidemiology,erasmus medical center,rotterdam, Netherlands, surgery department,university of otago,dunedin,new zealand,division of human genetics,national institute of genetics,mishima, Japan, neurosurgery of neurocenter,kuopio university hospital,kuopio, Finland, department of internal medicine,the university of texas medical school,houston,tx, United States, internal medicine,erasmus medical center,rotterdam, Netherlands, department of neurosurgery,helsinki university central hospital,helsinki, Finland, the sigfried and janet weis center for research,geisinger health system,danville,pa, United States, department of health,functional capacity and welfare,national institute for health and welfare,helsinki, Finland, department of surgery,temple university school of medicine,philadelphia,pa, United States, mayo clinic,rochester,ny,united states,surgery department,university of otago,dunedin, New Zealand, center for human genetics research,massachusetts general hospital,boston,ma,united states,medical and population genetics program,broad institute,boston,ma,united states,internal medicine,erasmus medical center,rotterdam, Netherlands, center for statistical genetics,baylor college of medicine,houston,tx, United States, department of medicine,university of mississippi medical center,jackson,ms, United States, department of surgery,yale school of medicine,new haven,ct, United States, department of surgery,yale school of medicine,new haven,ct, United States, department of neurosurgery,helsinki university central hospital,helsinki, Finland, department of neurology,university of california,san francisco,ca, United States, department of surgery,temple university school of medicine,philadelphia,pa, United States, center for human genetics research,vanderbilt university,nashville,tn, United States, section of hematology and oncology,department of medicine,university of chicagoil, United States, center for integrative medical sciences,riken,kanagawa, Japan, center for genetic medicine,northwestern university feinberg school of medicine,chicago,il, United States, department of preventive medicine,northwestern university feinberg school of medicine,chicago,il, United States, michael e. debakey department of surgery,baylor college of medicine,texas heart institute,houston,tx, United States, analytic and translational genetics unit,massachusetts general hospital and harvard medical school,boston,ma, United States, section of hematology and oncology,department of medicine,university of chicagoil, United States, hôpitaux universitaire de genève et,faculté de médecine de genève,geneva, Switzerland, department of neurology,university of cincinnati school of medicine,cincinnati,oh, United States, department of internal medicine,the university of texas medical school,houston,tx,united states,center for genetic medicine,northwestern university feinberg school of medicine,chicago,il, United States, analytic and translational genetics unit,massachusetts general hospital and harvard medical school,boston,ma, United States, hôpitaux universitaire de genève et,faculté de médecine de genève,geneva, Switzerland, radboud university medical center,radboud institute for health sciences,nijmegen, Netherlands, research division,essentia institute of rural health,duluth,mn, United States, department of cardiovascular sciences,nihr leicester cardiovascular biomedical research unit,university of leicester, United Kingdom, center for systems genomics,the pennsylvania state university,pennsylvania,pa,united states,department of biomedical sciences,stellenbosch university,tygerberg, South Africa, department of surgery,temple university school of medicine,philadelphia,pa, United States, center for human genetics research,massachusetts general hospital,boston,ma, United States, surgery department,university of otago,dunedin, New Zealand, analytic and translational genetics unit,massachusetts general hospital and harvard medical school,boston,ma, United States, department of internal medicine,the university of texas medical school,houston,tx, United States, research division,essentia institute of rural health,duluth,mn, United States, department of convergence medicine,university of ulsan college of medicine and asan institute for life sciences,asan medical center,seoul, South Korea, utrecht stroke center,department of neurology and neurosurgery,rudolf magnus institute of neuroscience, Netherlands, department of epidemiology,julius center for health sciences and primary care, Netherlands, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan, division of human genetics,national institute of genetics,mishima, Japan
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Authors
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