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 × 10-8). Single nucleotide polymorphisms comprising rs9675262 (near HS3ST3A1 and MIR548H3 genes, P = 1.15 × 10-7), rs9820240 (in DCLK3 gene, P = 2.23 × 10-7), rs10916409 (near ISCA1P2 gene, P = 4.55 × 10-6), and rs540422 (in PICALM gene, P = 9.68 × 10-6) 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.

中文翻译：

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全基因组关联研究无痴呆的老年人白质高血容量。

背景技术白质过高与认知障碍有关，其遗传预测因子仍不清楚。在这里，我们进行了全基因组关联研究，以确定与未痴呆的老年人中白质超高量（WMHV）相关的新型遗传决定因素。方法阿尔茨海默氏病神经影像学倡议研究队列中纳入了350名55-80岁的非西班牙裔白种人受试者。WMHV与遗传多态性的关联性在加性遗传模型下使用多元线性回归进行了探索。进行了进一步的研究，以探索遗传变异对认知相关表型的影响。结果HS3ST3A1和MIR548H3基因附近的Rs7220676与WMHV水平在全基因组意义上相关（P = 2.96×10-8）。包含rs9675262（在HS3ST3A1和MIR548H3附近，P = 1.15×10-7），rs9820240（在DCLK3基因中，P = 2.23×10-7），rs10916409（在ISCA1P2基因附近，P = 4.55×10-6）的单核苷酸多态性和rs540422（在PICALM基因中，P = 9.68×10-6）被确定为与WMHV水平相关的提示基因座。rs7220676（C）的次要等位基因以剂量依赖性方式与较低的log（WMHV）相关。此外，rs7220676与通过迷你精神状态检查和记忆评分评估的认知能力下降率相关。结论HS3ST3A1和MIR548H3基因附近的一个新基因座与WMHV水平有关，可能与神经退行性疾病有关。rs540422和rs540422（在PICALM基因中，P = 9.68×10-6）被确定为与WMHV水平相关的提示基因座。rs7220676（C）的次要等位基因呈剂量依赖性地与较低的log（WMHV）相关。此外，rs7220676与通过迷你精神状态检查和记忆评分评估的认知能力下降率相关。结论HS3ST3A1和MIR548H3基因附近的一个新基因座与WMHV水平有关，可能与神经退行性疾病有关。rs540422和rs540422（在PICALM基因中，P = 9.68×10-6）被确定为与WMHV水平相关的提示基因座。rs7220676（C）的次要等位基因以剂量依赖性方式与较低的log（WMHV）相关。此外，rs7220676与通过迷你心理状态检查和记忆评分评估的认知能力下降率相关。结论HS3ST3A1和MIR548H3基因附近的一个新基因座与WMHV水平有关，可能与神经退行性疾病有关。