Lancet Neurology:进行性核上性麻痹生存的遗传决定因素:一项全基因组关联研究

2021-02-21 网络 网络

进行性核上性麻痹(PSP)是一种快速发展的神经退行性疾病。在经典的PSP-Richardson综合征(PSP-RS)中,患者会出现平衡问题,经常跌倒,眼球功能障碍和痴呆。

进行性核上性麻痹(PSP)是一种快速发展的神经退行性疾病。在经典的PSP-Richardson综合征(PSP-RS)中,患者会出现平衡问题,经常跌倒,眼球功能障碍和痴呆,一般患者从症状出现起平均存活6.9年。在过去10年中定义的一些PSP亚型,如PSP-帕金森综合征和PSP-进行性步态冻结,与较慢的进展速度有关。先前研究表明,PSP表型通过TRIM11/17位点的变异而改变。在这项研究中,研究人员旨在确定PSP患者生存的遗传决定因素。

在这两阶段全基因组关联研究的第一阶段(GWAS),本研究纳入了根据病理学和临床标准诊断的PSP患者,其来自两个不同的队列:有来自梅奥诊所(美国佛罗里达州杰克逊维尔)和慕尼黑(德国)的脑库的2011年PSP GWAS队列;另一项为伦敦大学学院PSP队列研究,来自脑库和前瞻性研究,是一项针对非典型帕金森综合征患者的全英国纵向研究。本文利用GWAS平台的功能定位和注释评估了GWAS中通过全基因组显著性变体的表达数量性状位点(eQTL)谱,并利用eQTLGen和PsychENCODE数据集进行了共定位分析。

这项研究数据收集和分析时间为2016年8月1日至2020年2月1日。在第一阶段有1001名欧洲白人血统的PSP患者的数据。研究发现全基因组与12号染色体的存活率显著相关(单核苷酸多态性rs2242367,p=7.5 × 10-10,危险比1.42[95%CI 1.22-1.67])。rs2242367与第二阶段(n=238;p=0.049,1.22[1.00-1.48])和两个阶段的汇总分析(n=1239;p=1.3×10-10,1.37[1.25-1.51])的个体生存率相关。eQTL数据库筛选显示rs2242367与全血中LRRK2和两个长基因间非编码RNAs(lncRNAs)LINC0255和AC079630.4的表达增加有关。虽然本研究没有检测到LRRK2的共定位信号,但对eQTLGen血液数据集中LINC02555的PSP存活信号和eQTLs的分析显示,假设4的后验概率为0.77,这表明共定位是由单一共同的因果变异引起的。

综上所述,LRRK2基因座作为一个潜在的遗传决定因素在相关的tau病,即阿尔茨海默病、额颞叶变性和皮质基底部变性中的疾病进展和生存中具有重要意义。

Jabbari, EdwinMok, Kin Y. et al. Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study. The Lancet Neurology, Volume 20, Issue 2, 107 - 116

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    2021-08-24 yinhl1978
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    2021-10-29 howi
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  6. [GetPortalCommentsPageByObjectIdResponse(id=1976649, encodeId=a9c919e6649c5, content=<a href='/topic/show?id=acd4943925f' target=_blank style='color:#2F92EE;'>#进行性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94392, encryptionId=acd4943925f, topicName=进行性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=869698, createdName=ligang4439, createdTime=Sat Feb 27 23:48:51 CST 2021, time=2021-02-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1671051, encodeId=7b0016e10517d, content=<a href='/topic/show?id=bd58310846e' target=_blank style='color:#2F92EE;'>#决定因素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31084, encryptionId=bd58310846e, topicName=决定因素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e7726816052, createdName=wushaoling, createdTime=Thu Mar 11 01:48:51 CST 2021, time=2021-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2001244, encodeId=d57220012447f, content=<a href='/topic/show?id=d5df12695e6' target=_blank style='color:#2F92EE;'>#Neurol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12695, encryptionId=d5df12695e6, topicName=Neurol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8217292, createdName=yinhl1978, createdTime=Tue Aug 24 07:48:51 CST 2021, time=2021-08-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1831031, encodeId=ac1d183103101, content=<a href='/topic/show?id=1b6210686b2' target=_blank style='color:#2F92EE;'>#Lancet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10686, encryptionId=1b6210686b2, topicName=Lancet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f0227, createdName=howi, createdTime=Fri Oct 29 03:48:51 CST 2021, time=2021-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1342223, encodeId=74c71342223d8, content=<a href='/topic/show?id=62eb2939954' target=_blank style='color:#2F92EE;'>#全基因组关联研究#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29399, encryptionId=62eb2939954, topicName=全基因组关联研究)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Tue Feb 23 13:48:51 CST 2021, time=2021-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1546549, encodeId=f22715465493a, content=<a href='/topic/show?id=81eb2939373' target=_blank style='color:#2F92EE;'>#全基因组#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29393, encryptionId=81eb2939373, topicName=全基因组)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc2113925052, createdName=ms1692810954239974, createdTime=Tue Feb 23 13:48:51 CST 2021, time=2021-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1575773, encodeId=5ebb15e577321, content=<a href='/topic/show?id=11a894395e5' target=_blank style='color:#2F92EE;'>#进行性核上性麻痹#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94395, encryptionId=11a894395e5, topicName=进行性核上性麻痹)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a8016187090, createdName=lilili1109, createdTime=Tue Feb 23 13:48:51 CST 2021, time=2021-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1034176, encodeId=2c5c10341e65d, content=顶刊就是不一样,质量很高,内容精彩!学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=goodbing, createdTime=Mon Feb 22 01:48:51 CST 2021, time=2021-02-22, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1976649, encodeId=a9c919e6649c5, content=<a href='/topic/show?id=acd4943925f' target=_blank style='color:#2F92EE;'>#进行性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94392, encryptionId=acd4943925f, topicName=进行性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=869698, createdName=ligang4439, createdTime=Sat Feb 27 23:48:51 CST 2021, time=2021-02-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1671051, encodeId=7b0016e10517d, content=<a href='/topic/show?id=bd58310846e' target=_blank style='color:#2F92EE;'>#决定因素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31084, encryptionId=bd58310846e, topicName=决定因素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e7726816052, createdName=wushaoling, createdTime=Thu Mar 11 01:48:51 CST 2021, time=2021-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2001244, encodeId=d57220012447f, content=<a href='/topic/show?id=d5df12695e6' target=_blank style='color:#2F92EE;'>#Neurol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12695, encryptionId=d5df12695e6, topicName=Neurol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8217292, createdName=yinhl1978, createdTime=Tue Aug 24 07:48:51 CST 2021, time=2021-08-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1831031, encodeId=ac1d183103101, content=<a href='/topic/show?id=1b6210686b2' target=_blank style='color:#2F92EE;'>#Lancet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10686, encryptionId=1b6210686b2, topicName=Lancet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f0227, createdName=howi, createdTime=Fri Oct 29 03:48:51 CST 2021, time=2021-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1342223, encodeId=74c71342223d8, content=<a href='/topic/show?id=62eb2939954' target=_blank style='color:#2F92EE;'>#全基因组关联研究#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29399, encryptionId=62eb2939954, topicName=全基因组关联研究)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Tue Feb 23 13:48:51 CST 2021, time=2021-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1546549, encodeId=f22715465493a, content=<a href='/topic/show?id=81eb2939373' target=_blank style='color:#2F92EE;'>#全基因组#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29393, encryptionId=81eb2939373, topicName=全基因组)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc2113925052, createdName=ms1692810954239974, createdTime=Tue Feb 23 13:48:51 CST 2021, time=2021-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1575773, encodeId=5ebb15e577321, content=<a href='/topic/show?id=11a894395e5' target=_blank style='color:#2F92EE;'>#进行性核上性麻痹#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94395, encryptionId=11a894395e5, topicName=进行性核上性麻痹)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a8016187090, createdName=lilili1109, createdTime=Tue Feb 23 13:48:51 CST 2021, time=2021-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1034176, encodeId=2c5c10341e65d, content=顶刊就是不一样,质量很高,内容精彩!学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=goodbing, createdTime=Mon Feb 22 01:48:51 CST 2021, time=2021-02-22, status=1, ipAttribution=)]
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    2021-02-22 goodbing

    顶刊就是不一样,质量很高,内容精彩!学到很多

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