Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux.
Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux.
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DOI：
10.1038/s41598-017-15062-9
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发表时间：
2017-11-06
影响因子：
4.6
通讯作者：
Cordell HJ
中科院分区：
文献类型：
--
作者：
Darlow JM;Darlay R;Dobson MG;Stewart A;Charoen P;Southgate J;Baker SC;Xu Y;Hunziker M;Lambert HJ;Green AJ;Santibanez-Koref M;Sayer JA;Goodship THJ;Puri P;Woolf AS;Kenda RB;Barton DE;Cordell HJ
膀胱输尿管反流(VUR)是儿童最常见的泌尿系统异常。尽管治疗方法有所改进，相关的肾脏病变--先天性发育不良、后天性疤痕或两者兼而有之--是儿童高血压和肾功能衰竭的常见原因。原发VUR是家族性的，传播率和兄弟姐妹风险都接近50%，并且表现出高度的遗传异质性。它经常与其他尿路发育异常有关，强调其病因为泌尿生殖道发育障碍。我们在三个欧洲人群中进行了全基因组连锁和关联研究，以寻找VUR的易感基因。1098个亲子三元组的家庭关联分析以及1147个病例和3789个对照的病例/对照关联分析没有显示任何令人信服的关联，但在显性模型下对460个家庭(1062个患病个体)进行的参数连锁分析发现，10q26上有一个区域显示出与VUR的强连锁(HLOD=4.90；ZLRLOD=4.39)。~9Mb区包含69个基因，其中包括一些很好的生物候选基因。在选定的个体中对这一区域进行重新测序并没有明显地涉及任何基因，但FOXI2、FANK1和GLRX3仍然是进一步研究的候选基因。这是迄今为止对VUR进行的最大规模的遗传学研究，突出了10q26区域是欧洲人群VUR的主要遗传贡献者。
Vesicoureteric reflux (VUR) is the commonest urological anomaly in children. Despite treatment improvements, associated renal lesions – congenital dysplasia, acquired scarring or both – are a common cause of childhood hypertension and renal failure. Primary VUR is familial, with transmission rate and sibling risk both approaching 50%, and appears highly genetically heterogeneous. It is often associated with other developmental anomalies of the urinary tract, emphasising its etiology as a disorder of urogenital tract development. We conducted a genome-wide linkage and association study in three European populations to search for loci predisposing to VUR. Family-based association analysis of 1098 parent-affected-child trios and case/control association analysis of 1147 cases and 3789 controls did not reveal any compelling associations, but parametric linkage analysis of 460 families (1062 affected individuals) under a dominant model identified a single region, on 10q26, that showed strong linkage (HLOD = 4.90; ZLRLOD = 4.39) to VUR. The ~9Mb region contains 69 genes, including some good biological candidates. Resequencing this region in selected individuals did not clearly implicate any gene but FOXI2, FANK1 and GLRX3 remain candidates for further investigation. This, the largest genetic study of VUR to date, highlights the 10q26 region as a major genetic contributor to VUR in European populations.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
GUDMAP数据库 - 用于泌尿生殖器研究的在线资源。
DOI：
10.1242/dev.063594
发表时间：
2011-07
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Harding SD;Armit C;Armstrong J;Brennan J;Cheng Y;Haggarty B;Houghton D;Lloyd-MacGilp S;Pi X;Roochun Y;Sharghi M;Tindal C;McMahon AP;Gottesman B;Little MH;Georgas K;Aronow BJ;Potter SS;Brunskill EW;Southard-Smith EM;Mendelsohn C;Baldock RA;Davies JA;Davidson D
通讯作者：
Davidson D
影响因子：
5.8
作者：
Derkach, Andriy;Chiang, Theodore;Strug, Lisa J.
通讯作者：
Strug, Lisa J.
影响因子：
2.1
作者：
Abreu, PC;Hodge, SE;Greenberg, DA
通讯作者：
Greenberg, DA