NOTCH3 variants are common in the general population and associated with stroke and vascular dementia: an analysis of 200,000 participants
NOTCH3 variants are common in the general population and associated with stroke and vascular dementia: an analysis of 200,000 participants
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NOTCH3 变异在普通人群中很常见，并与中风和血管性痴呆相关：对 200,000 名参与者的分析
DOI：
10.1101/2020.12.14.20248151
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Cho B
中科院分区：
文献类型：
--
作者：
Cho B
BackgroundCysine-alteringNOTCH 3变种相同的那些导致罕见的单基因形式的中风，CADASIL，已被报道比预期的更常见在一般人群中，但其临床意义和中风和痴呆症的风险在community. MethodsCysine-alteringNOTCH 3变种的贡献仍不清楚在英国生物银行全外显子组测序数据（N= 200，632）。比较变异携带者和非携带者的中风、痴呆和CADASIL的其他临床特征的频率，以及MRI白色高信号体积。从那些变异的MRI进行了视觉评级，每个匹配的三个controls.ResultsOf 200，632参与者与外显子组测序数据可用，443（450人中有101人）进行了67个不同的半胱氨酸alteringNOTCH 3变异。校正年龄、性别和祖先主成分后，NOTCH 3变异携带者中风风险增加（OR：2.33，p=0.0003），血管性痴呆（OR：5.03，p=0.007），WMH体积增加（标准化差异：0.52，p<0.001），和白色超微结构损伤的DTI-PSMD（标准化差异：0.71，p<0.001）。对47名携带者和148名匹配对照者的MRI进行视觉分析，发现变异与腔隙（OR：4.83，p<0.001）和脑微出血（OR：3.61，p<0.001）的存在相关。WMH患病率在前颞叶（OR：6.92，p<0.001）和外囊（OR：12.44，p<0. 001. ConclusionsCysteine-changing NOTCH 3 variants are common in the general population and are risk factors for apparently“散发性”stroke and vascular dementia.它们与SVD的MRI变化相关，分布与CADASIL中观察到的分布相似。
BackgroundCysteine-alteringNOTCH3variants identical to those causing the rare monogenic form of stroke, CADASIL, have been reported more common than expected in the general population, but their clinical significance and contribution to stroke and dementia risk in the community remains unclear.MethodsCysteine-alteringNOTCH3variants were identified in UK Biobank whole-exome sequencing data (N=200,632). Frequency of stroke, dementia and other clinical features of CADASIL, and MRI white matter hyperintensity volume were compared between variant carriers and non-carriers. MRIs from those with variants were visually rated, each matched with three controls.ResultsOf 200,632 participants with exome sequencing data available, 443 (∼1 in 450) carried 67 different cysteine-alteringNOTCH3variants. After adjusting for age, sex, and ancestry principal components,NOTCH3variant carriers had increased risk of stroke (OR: 2.33, p=0.0003), and vascular dementia (OR: 5.03, p=0.007), and increased WMH volume (standardised difference: 0.52, p<0.001), and white matter ultrastructural damage on DTI-PSMD (standardised difference: 0.71, p<0.001). On visual analysis of MRIs from 47 carriers and 148 matched controls, variants were associated with presence of lacunes (OR: 4.83, p<0.001) and cerebral microbleeds (OR: 3.61, p<0.001). WMH prevalence was most increased in the anterior temporal lobes (OR: 6.92, p<0.001) and external capsule (OR: 12.44, p<0.001).ConclusionsCysteine-changingNOTCH3variants are common in the general population and are risk factors for apparently “sporadic” stroke and vascular dementia. They are associated with MRI changes of SVD, in a distribution similar to that seen in CADASIL.
基因组风险评分提供的预测性能可与缺血性中风的临床危险因素相媲美
DOI：
10.1101/689935
发表时间：
2019
期刊：
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影响因子：
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作者：
Abraham G
通讯作者：
Abraham G
CADASIL 中 MRI 病变体积的遗传力
DOI：
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发表时间：
2006
期刊：
影响因子：
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作者：
ChristianOpherk;NilsPeters;MarkusHoltmannspötter;AndreasGschwendtner;BertramMüller;MartinDichgans
通讯作者：
MartinDichgans