老年人非痴呆患者脑白质高信号体积的全基因组关联研究。
Genome-wide association study of white matter hyperintensity volume in elderly persons without dementia.
机构信息
Department of Neurology, Qingdao Municipal Hospital affiliated to Qingdao University, Qingdao, China.
Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai 200040, China.
出版信息
Neuroimage Clin. 2020;26:102209. doi: 10.1016/j.nicl.2020.102209. Epub 2020 Feb 6.
BACKGROUND
White matter hyperintensity has been correlated with cognitive disorders and its genetic predictors remain unclear. Here we conducted a genome-wide association study to identify novel genetic determinants that were correlated with white matter hyperintensity volume (WMHV) among non-demented elders.
METHODS
Three hundred and fifty non-Hispanic Caucasian subjects aged 55-80 years were included from the Alzheimer's Disease Neuroimaging Initiative cohort. Associations of WMHV with genetic polymorphisms were explored using multiple linear regression under an additive genetic model. Further studies were conducted to explore the influence of genetic variants on cognition-related phenotypes.
RESULTS
Rs7220676 near HS3ST3A1 and MIR548H3 genes was associated with WMHV levels at genome-wide significance (P = 2.96 × 10). Single nucleotide polymorphisms comprising rs9675262 (near HS3ST3A1 and MIR548H3 genes, P = 1.15 × 10), rs9820240 (in DCLK3 gene, P = 2.23 × 10), rs10916409 (near ISCA1P2 gene, P = 4.55 × 10), and rs540422 (in PICALM gene, P = 9.68 × 10) were identified as suggestive loci linked to WMHV levels. The minor allele of rs7220676 (C) showed association with lower log (WMHV) in a dose-dependent manner. Besides, rs7220676 was correlated with rates of cognitive decline assessed by Mini-mental State Examination and memory scores.
CONCLUSIONS
A novel locus near HS3ST3A1 and MIR548H3 genes was associated with WMHV levels and it may be involved in neurodegenerative diseases.
背景
脑白质高信号与认知障碍有关，但其遗传预测因素仍不清楚。本研究进行了全基因组关联研究，以确定与非痴呆老年人脑白质高信号体积（WMHV）相关的新的遗传决定因素。
方法
从阿尔茨海默病神经影像学倡议队列中纳入 355 名年龄在 55-80 岁之间的非西班牙裔白种人。采用加性遗传模型下的多元线性回归，研究 WMHV 与遗传多态性的相关性。进一步研究遗传变异对认知相关表型的影响。
结果
位于 HS3ST3A1 和 MIR548H3 基因附近的 rs7220676 与 WMHV 水平呈全基因组显著相关（P=2.96×10-8）。包含 rs9675262（位于 HS3ST3A1 和 MIR548H3 基因附近，P=1.15×10-8）、rs9820240（位于 DCLK3 基因，P=2.23×10-8）、rs10916409（位于 ISCA1P2 基因附近，P=4.55×10-8）和 rs540422（位于 PICALM 基因，P=9.68×10-8）的单核苷酸多态性被确定为与 WMHV 水平相关的提示性位点。rs7220676 的次要等位基因（C）呈剂量依赖性与较低的 log（WMHV）相关。此外，rs7220676 与 Mini-mental State Examination 评估的认知衰退率和记忆评分相关。
结论
位于 HS3ST3A1 和 MIR548H3 基因附近的一个新基因座与 WMHV 水平相关，可能与神经退行性疾病有关。
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