Circulation:腹主动脉瘤的新增基因风险位点!

2020-10-31 Xiaozeng MedSci原创

腹主动脉瘤(AAA)是导致心血管疾病死亡的重要原因;然而,其遗传决定因素仍未完全确定。总体上,10个已确定的风险位点只解释了一小部分的AAA遗传贡献。

腹主动脉瘤(AAA)是导致血管疾病死亡的重要原因;然而,其遗传决定因素仍未完全确定。总体上,10个已确定的风险位点只解释了一小部分的AAA遗传贡献。

Klarin等人在7642例AAA和172172对照共约1800万个DNA序列变异中进行了全基因组关联分析。并通过孟德尔随机分析以检测血压对AAA的因果效应。研究人员还检测了AAA风险变异与其他部位(下肢、脑)动脉瘤的关联,并开发了一种全基因组多基因风险评分(PRS)来筛选AAA高危人群。

研究设计

通过全基因组关联分析,研究人员共鉴定出14个新位点,使已知的显著AAA位点增加到了24个。在本次孟德尔随机分析中,研究人员证明了一个基因将舒张压升高了10 mmHg(优势比 1.43),对收缩压无明显影响(优势比 1.06),可能与AAA发展有因果关系。

吸烟和血压孟德尔随机分析

此外,24个AAA风险变异中有19个与至少其他一处的动脉瘤相关。一种纳入29个变异的PRS与AAA显著相关(优势比 1.26),且独立于家族史和吸烟风险因素之外。

与各部位动脉瘤相关的基因

采用该PRS,研究人员鉴定出一个AAA发病率高于现有指南筛选试验中观察到的亚群。

AAA的全基因组多基因风险评分

总之,该研究发现了多个与AAA治疗相关的新基因,并确定了一个亚群,该群体罹患AAA的风险显著增加,且与家族史无关。

原始出处:

Derek Klarin, et al. Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program. Circulation. 2020;142:1633–1646

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    2020-11-03 咻凡

    腹主动脉瘤(AAA)是导致心血管疾病死亡的重要原因;然而,其遗传决定因素仍未完全确定。总体上,10个已确定的风险位点只解释了一小部分的AAA遗传贡献。

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1716273, encodeId=50bf1e1627396, content=<a href='/topic/show?id=cef041932e1' target=_blank style='color:#2F92EE;'>#基因风险位点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41932, encryptionId=cef041932e1, topicName=基因风险位点)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a3532191669, createdName=jiyangfei, createdTime=Sat Feb 20 07:42:59 CST 2021, time=2021-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1704505, encodeId=90351e0450550, content=<a href='/topic/show?id=1f5b41931ce' target=_blank style='color:#2F92EE;'>#基因风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41931, encryptionId=1f5b41931ce, topicName=基因风险)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb0530750602, createdName=hmwwww, createdTime=Mon Apr 05 20:42:59 CST 2021, time=2021-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=896627, encodeId=6e3d89662e98, content=腹主动脉瘤(AAA)是导致心血管疾病死亡的重要原因;然而,其遗传决定因素仍未完全确定。总体上,10个已确定的风险位点只解释了一小部分的AAA遗传贡献。, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b58d5402080, createdName=咻凡, createdTime=Tue Nov 03 15:30:48 CST 2020, time=2020-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=896523, encodeId=a3ad8965232b, content=24个AAA风险变异中有19个与至少其他一处的动脉瘤相关。, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ae205385871, createdName=Lexi, createdTime=Tue Nov 03 10:39:23 CST 2020, time=2020-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1415703, encodeId=541f1415e036e, content=<a href='/topic/show?id=04812314540' target=_blank style='color:#2F92EE;'>#主动脉#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23145, encryptionId=04812314540, topicName=主动脉)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=77603112682, createdName=circumcision, createdTime=Mon Nov 02 06:42:59 CST 2020, time=2020-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1429069, encodeId=6c79142906995, content=<a href='/topic/show?id=ee192321560' target=_blank style='color:#2F92EE;'>#主动脉瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23215, encryptionId=ee192321560, topicName=主动脉瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=95e34160730, createdName=fengting4, createdTime=Mon Nov 02 06:42:59 CST 2020, time=2020-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=895877, encodeId=c0ad8958e7e6, content=<a href='/topic/show?id=77d9855258f' target=_blank style='color:#2F92EE;'>#腹主动脉瘤#</a>与基因有关?可靠性不大吧, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85525, encryptionId=77d9855258f, topicName=腹主动脉瘤)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Sat Oct 31 15:58:55 CST 2020, time=2020-10-31, status=1, ipAttribution=)]
    2020-11-03 Lexi

    24个AAA风险变异中有19个与至少其他一处的动脉瘤相关。

    0

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    2020-10-31 lovetcm

    #腹主动脉瘤#与基因有关?可靠性不大吧

    0

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