全基因组关联研究Gilles de la图雷特综合症(S32.006)

文摘

摘要目的:识别常见的遗传变异与Gilles de la图雷特综合症(GTS)。

背景GTS是一个高度遗传、神经发育障碍,尽管发现明确的GTS易感基因是具有挑战性的。在这里,我们报告的第一个全基因组关联研究(GWAS) 1496例和5249 GTS的选择,ancestry-matched控制。

设计/方法:多中心病例对照研究,有欧洲血统的话题,(欧盟),两个欧产种群隔离,德系犹太人(AJ)和法国加拿大人(FC),和两个紧密拉丁美洲人口从安蒂奥基亚省隔离,哥伦比亚(ANT)和哥斯达黎加(CVCR)的中央山谷。使用DSM-IV-TR条件进行了诊断。908年欧盟的情况下,所有population-isolate情况下,298年欧盟控制和FC和ANT控制都是基因分型的Illumina公司Hap610平台。额外的148年欧盟例IlluminaHap370基因分型,和剩余的欧盟和AJ控制以前Illumina公司Hap550K基因分型和Hap1M数组。质量控制(QC)与特定的关注是在叮铃声进行删除snp基因分型结果与微分表现在平台。Ancestry-stratified叮铃声使用逻辑回归的病例对照分析。在金属Case-weighted进行了荟萃分析。

结果:和结论:欧产样品的主元分析(欧盟,AJ, FC),没有全基因组位点超过了阈值的意义(p < 5 x10⁸)。然而,前535位点(p < 0.001)明显丰富的遗传变异与基因表达在额叶皮层有关,与假设一致的是,GTS起源于fronto-striatal电路的失调。第二个荟萃分析包括拉丁美洲的样本中发现了一个轨迹COL27A19 (rs7868992)染色体上的基因与基因组重要假定值= 2.9 x 10⁸。额外的神经发育基因的兴趣包括顶部信号SLITRK6,CNTN1,SEMA3G。

结论:复制在额外的样品正在进行中,以验证研究结果并确定额外的GTS易感性位点。

支持:从犹大基金会的资助,国家卫生研究院的基金NS40024 DLP和图雷特综合症协会国际财团遗传学、NIH格兰特NS16648和DLP妥瑞症协会的资助,NIH NS037484 NBF, NIH资助NS043538 AR-L,美国神经病学学会的基金会和国家卫生研究院格兰特MH085057 JMS。首页

披露:Scharf博士没有披露。Yu博士没有披露。马修斯博士没有披露。尼尔博士没有披露。Stewart博士没有披露。Fagerness博士没有披露。Scharf博士没有披露。Scharf博士没有披露。Scharf博士没有披露。Osiecki博士没有披露。 Dr. Illmann has nothing to disclose. Dr. Cath has nothing to disclose. Dr. King has nothing to disclose. Dr. Dion has received personal compensation for activities with Biovail Pharma, Pfizer and Eli Lilly. Dr. Sandor has received personal compensation for activities with Psyadon, Shire, Solway, UCB Pharma, Janssen, Eli Lilly, Pfizer, and Prestwick. Dr. Barr has nothing to disclose. Dr. Budman has received research support from Psyadon Pharmaceuticals and Otsuka Pharmaceuticals. Dr. Lyon has nothing to disclose. Dr. Hoekstra has received personal compensation for activities with Desitin, Eli Lilly & Company and Shire. Dr. Singer has nothing to disclose. Dr. Jankovic has received personal compensation for activities with Allergan, Inc., Chelsea Therapeutics, Serono Inc., Merz Pharma, Lundbeck Research USA, Inc, Teva Neuroscience as a consultant. Dr. Jankovic has received personal compensation in an editorial capacity for Medlink: Neurology in Clinical Practice. Dr. Jankovic has received research support from Allergan, Inc, Allon Therapeutics, Ceregene, Inc., Chelsea Therapeutics; Diana Helis Henry Medical Research Foundation, Serono Inc., Huntington's Disease Society of America, Huntington Study Group, Impax Pharmaceuticals, Ipsen Limited, Lundbeck Research USA, Inc. Dr. Gilbert has received personal compensation in an editorial capacity for Pediatrics Review and Education Program R11. Dr. Gilbert has received research support from Psyadon Pharmaceuticals and Otsuka Pharmaceuticals. Dr. Hoekstra has received personal compensation for activities with Desitin, Eli Lilly & Company and Shire. Dr. Heiman has nothing to disclose. Dr. Tischfield has nothing to disclose. Dr. State has nothing to disclose. Dr. Robertson has nothing to disclose. Dr. Kurlan has nothing to disclose. Dr. Ophoff has nothing to disclose. Dr. Gibbs has nothing to disclose. Dr. Cookson has nothing to disclose. Dr. Hardy has nothing to disclose. Dr. Singleton has nothing to disclose. Dr. Rodriguez has nothing to disclose. Dr. Rouleau has nothing to disclose. Dr. Heutink has nothing to disclose. Dr. Oostra has nothing to disclose. Dr. McMahon has nothing to disclose. Dr. Freimer has nothing to disclose. Dr. COX has nothing to disclose. Dr. Pauls has nothing to disclose.