Genome‐wide association study identifies two novel chromosome loci associated with cerebral white matter hyperintensity volume in Japanese population Genetics/genetics of cognitive aging

• Published in: Alzheimer's & dementia Vol. 16; no. S3
• Main Authors: Kokubo, Manabu, Ozaki, Kouichi, Ohta, Hidetaka, Nakanishi, Hiroki, Shimizu, Atsuya, Arai, Hidenori, Sakurai, Takashi
• Format: Journal Article
• Language: English
• Published: 01.12.2020
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.041342

Abstract Background Cerebral white matter hyperintensity (WMH) is highly prevalent in the elderly population, and increases the risk of dementia and stroke . The genetic underpinnings of WMH are still incompletely characterized, especially in Asian. To identify novel genetic variants influencing WMH burden, we conducted a genome‐wide association studies (GWAS) in Japanese population. Method We included outpatients who visited National Center for Geriatrics and Gerontology (NCGG) without symptomatic heart failure, ischemic heart disease, atrial fibrillation or stroke. The clinical data and blood samples used in this study were distributed from the NCGG Biobank, which collects and stores biological material and associated clinical information for biomedical research. WMH volume were analyzed by an automatic segmentation application (SNIPER). To identify WMH associated loci, we conducted a GWAS with linear regression analysis adjusted with age and gender as covariates using approximately 4,300,000 single nucleotide polymorphisms (SNP) imputed based on reference panel from large Japanese sequences. This study was approved by the Ethics Review Board of NCGG. Result A total of 813 patients were enrolled in the present study (mean age 75.4 ± 8.1 years), including 503 female patients (61.9%). The clinical profiles of the study participants are normal control: n = 184; Alzheimer’s disease: n = 375; other: n = 254. The mean MMSE score was 24.2 ± 4.5.In the GWAS, we have identified two novel loci on chromosome 1 and 2 associated with WMH volume with GWAS significance (P < 5 × 10‐8). We also identified several WMH volume associated loci with suggestive significance (P < 1 × 10‐6). Conclusion This GWAS of WMH burden in outpatients of our hospital identifies 2 novel genetic loci with GWAS significance and several candidate loci. This is the first report on WMH associated loci of Japanese population. Further characterization of these loci may provide novel insights into the pathogenesis of cerebral WMH in Japanese population.