Nat. Rev Neurosci:对435563人酒精使用问题进行全基因组meta分析,深入了解生物学以及与其他性状的关系

2020-07-16 MedSci原创 MedSci原创

酗酒是世界范围内导致死亡和残疾的主要原因。虽然全基因组关联研究已经确定了PAU的危险基因,但这一特性的遗传结构尚未完全了解。

酒精使用和酒精使用障碍(AUD)是世界范围内导致死亡和残疾的主要原因。对AUD的全基因组关联研究通过不同的评估方法确定了在欧洲人群中存在的潜在危险基因。在多个研究中被定位到几个危险基因的变体包括ADH1B(醇脱氢酶1B(class I)、β多肽)、ADH1C(醇脱氢酶1C(class I)、γ多肽)、ALDH2(醛脱氢酶2家族成员,但仅在一些亚洲样本中)、SLC39A8、GCKR(葡萄糖激酶)和CRHR1(促肾上腺皮质激素释放激素受体1)。

方法:作者对435563名欧洲个体进行了PAU(酗酒)meta分析,将酒精使用障碍和饮酒问题结合起来。数据库集包括MVP,PGC和UKB数据集。利用GWAS(MTAG),对来自GSCAN的PAU和DrnkWk进行了多性状分析。使用多基因风险评分-连续收缩(PRS-CS)60对BioVU所有欧洲血统(n=67588)基因型个体进行多基因评分。PRS-CS使用贝叶斯框架从外部参考集建立连锁不平衡模型,以及SNP效应大小的连续收缩。

结果:作者发现了29个独立的风险变异,其中19个是新的。PAU与138个表型(包括物质使用和精神病特征)存在遗传相关。在一个独立的生物库样本(BioVU,n=67589)中进行的全表型多基因风险评分分析证实了PAU与药物使用和精神疾病之间的遗传相关。PAU的遗传力在脑区、保守区和调节区均有丰富的遗传力。孟德尔随机化提示药物使用、精神状态、冒险行为和认知能力对PAU的易患性有因果关系。 16个基因与325种药物之间的特殊相互作用可能为开发治疗PAU的药物提供靶点。潜在的靶点包括D2多巴胺受体(由DRD2编码)和磷酸二酯酶4B(由PDE4B编码)。这些位点的风险变异也表明它们可能是“精确医学”的靶标。

原文链接:

Zhou, H., Sealock, J.M., Sanchez-Roige, S. et al. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traitsNat Neurosci23, 809–818 (2020). https://doi.org/10.1038/s41593-020-0643-5

 

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    2020-08-04 liye789132251
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    2021-04-22 一闲
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    2020-11-23 guojianrong
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    2020-07-18 lsndxfj
  5. [GetPortalCommentsPageByObjectIdResponse(id=1884461, encodeId=24e4188446172, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Aug 04 20:22:44 CST 2020, time=2020-08-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896700, encodeId=0d1d1896e0023, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Thu Apr 22 16:22:44 CST 2021, time=2021-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888173, encodeId=e52d18881e3a0, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Mon Nov 23 22:22:44 CST 2020, time=2020-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1364625, encodeId=219d1364625d5, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Sat Jul 18 13:22:44 CST 2020, time=2020-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1546528, encodeId=b1ae1546528c2, 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=25, 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=Sat Jul 18 13:22:44 CST 2020, time=2020-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1617920, encodeId=f5f0161e92089, content=<a href='/topic/show?id=e88f6930185' target=_blank style='color:#2F92EE;'>#生物学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69301, encryptionId=e88f6930185, topicName=生物学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e44019811593, createdName=12498c32m74暂无昵称, createdTime=Sat Jul 18 13:22:44 CST 2020, time=2020-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=803132, encodeId=fdb280313221, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4cb15400991, createdName=飞翔, createdTime=Fri Jul 17 20:38:03 CST 2020, time=2020-07-17, status=1, ipAttribution=)]
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    2020-07-17 飞翔

    学习了

    0

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