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Intracranial aneurysm risk locus 5q23.2 is associated with elevated systolic blood pressure
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نویسنده
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gaál e.i. ,salo p. ,kristiansson k. ,rehnström k. ,kettunen j. ,sarin a.-p. ,niemelä m. ,jula a. ,raitakari o.t. ,lehtimäki t. ,eriksson j.g. ,widen e. ,günel m. ,kurki m. ,von und zu fraunberg m. ,jääskeläinen j.e. ,hernesniemi j. ,järvelin m.-r. ,pouta a. ,newton-cheh c. ,salomaa v. ,palotie a. ,perola m.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 3
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چکیده
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Although genome-wide association studies (gwas) have identified hundreds of complex trait loci,the pathomechanisms of most remain elusive. studying the genetics of risk factors predisposing to disease is an attractive approach to identify targets for functional studies. intracranial aneurysms (ia) are rupture-prone pouches at cerebral artery branching sites. ia is a complex disease for which gwas have identified five loci with strong association and a further 14 loci with suggestive association. to decipher potential underlying disease mechanisms,we tested whether there are ia loci that convey their effect through elevating blood pressure (bp),a strong risk factor of ia. we performed a meta-analysis of four population-based finnish cohorts (n fin = 11 266) not selected for ia,to assess the association of previously identified ia candidate loci (n = 19) with bp. we defined systolic bp (sbp),diastolic bp,mean arterial pressure,and pulse pressure as quantitative outcome variables. the most significant result was further tested for association in the icbp-gwas cohort of 200 000 individuals. we found that the suggestive ia locus at 5q23.2 in prdm6 was significantly associated with sbp in individuals of european descent (p fin = 3.01e-05,p icbp-gwas = 0.0007,p all = 8.13e-07). the risk allele of ia was associated with higher sbp. prdm6 encodes a protein predominantly expressed in vascular smooth muscle cells. our study connects a complex disease (ia) locus with a common risk factor for the disease (sbp). we hypothesize that common variants in prdm6 can contribute to altered vascular wall structure,hence increasing sbp and predisposing to ia. true positive associations often fail to reach genome-wide significance in gwas. our findings show that analysis of traditional risk factors as intermediate phenotypes is an effective tool for deciphering hidden heritability. further,we demonstrate that common disease loci identified in a population isolate may bear wider significance. © 2012 gaál et al.
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آدرس
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public health genomics unit,department of chronic disease prevention,national institute for health and welfare,helsinki,finland,institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,department of neurosurgery,helsinki university central hospital,helsinki, Finland, public health genomics unit,department of chronic disease prevention,national institute for health and welfare,helsinki, Finland, public health genomics unit,department of chronic disease prevention,national institute for health and welfare,helsinki,finland,institute for molecular medicine finland (fimm),university of helsinki,helsinki, Finland, institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,the wellcome trust sanger institute,hinxton, United Kingdom, public health genomics unit,department of chronic disease prevention,national institute for health and welfare,helsinki,finland,institute for molecular medicine finland (fimm),university of helsinki,helsinki, Finland, public health genomics unit,department of chronic disease prevention,national institute for health and welfare,helsinki,finland,institute for molecular medicine finland (fimm),university of helsinki,helsinki, Finland, department of neurosurgery,helsinki university central hospital,helsinki, Finland, public health genomics unit,department of chronic disease prevention,national institute for health and welfare,helsinki, Finland, research centre of applied and preventive cardiovascular medicine,university of turku,turku,finland,department of clinical physiology,university of turku and turku university hospital,turku, Finland, department of clinical chemistry,university of tampere and tampere university hospital,tampere, Finland, diabetes unit,department of chronic disease prevention,national institute for health and welfare,helsinki,finland,department of general practice and primary health care,institute of clinical medicine,university of helsinki,helsinki,finland,vasa central hospital,vasa,finland,folkhälsan research centre,helsinki,finland,unit of general practice,helsinki university central hospital,helsinki, Finland, institute for molecular medicine finland (fimm),university of helsinki,helsinki, Finland, department of neurosurgery,yale university school of medicine,new haven,ct, United States, neurosurgery of neurocenter,kuopio university hospital,kuopio, Finland, neurosurgery of neurocenter,kuopio university hospital,kuopio, Finland, neurosurgery of neurocenter,kuopio university hospital,kuopio, Finland, department of neurosurgery,helsinki university central hospital,helsinki, Finland, department of biostatistics and epidemiology,school of public health,faculty of medicine,imperial college,london,united kingdom,institute of health sciences,university of oulu,oulu,finland,biocenter oulu,university of oulu,oulu,finland,department of children,young people and families,national institute for health and welfare,oulu, Finland, department of children,young people and families,national institute for health and welfare,oulu, Finland, center for human genetic research,cardiovascular research center,massachusetts general hospital,boston,ma,united states,program in medical and population genetics,broad institute of harvard and mit,cambridge,ma, United States, chronic disease epidemiology and prevention unit,department of chronic disease prevention,national institute for health and welfare,helsinki, Finland, institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,the wellcome trust sanger institute,hinxton,united kingdom,program in medical and population genetics and genetic analysis platform,broad institute of harvard and mit,cambridge,ma,united states,department of medical genetics,university of helsinki and university central hospital,helsinki, Finland, public health genomics unit,department of chronic disease prevention,national institute for health and welfare,helsinki,finland,institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,university of tartu,estonian genome centre,tartu, Estonia
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Authors
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