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• W4281781421 abstract "The genetic characteristics and correlations of hippocampal volume and plasm Aβ, probable endophenotypes for dementia, remain to be explored in Chinese community cohort. Using whole-exome sequencing and SNP-array genotyping, we sought to identify rare and common variants and genes influencing these two endophenotypes, and calculate their heritability and genetic correlation.Association analyses with both whole-exome sequencing and SNP-array genotyping data were performed for hippocampal volumes and plasm Aβ with mixed-effect linear regression model adjusted for sex, age, and total intracranial volume or APOE ε4 while considering familial relatedness. We also performed gene-level analysis for common and gene-burden analysis for rare variants. Heritability and genetic correlation were further examined.Totally 1,261 participants from a Chinese community cohort were included and we identified one gene, PTPRT, for hippocampal volume, with the top significant SNPs by whole genome-wide association study. rs6030076 (P=5.48×10-8, β=-0.092, SE=0.017) from whole-exome sequencing and rs6030088 (P=8.24×10-9, β=-105.22 SE=18.09) from SNP-array data, both located in this gene. Gene-burden analysis based on rare mutations detected 6 genes to be significantly associated with Aβ. The SNP-based heritability was 0.43±0.13 for hippocampal volume and 0.2-0.3 for plasma Aβ. The SNP-based genetic correlation between hippocampal volume and plasma Aβ were negative.In this study, we identified several SNPs and one gene, PTPRT, which were not reported in previous GWASs, associated with hippocampal volume. Besides, the heritability and the genetic correlation gave an overview of hippocampal volume and plasma Aβ. Our findings provide insights into the mechanisms behind the individual variances in these endophenotypes." @default.
• W4281781421 created "2022-06-13" @default.
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• W4281781421 date "2022-07-19" @default.
• W4281781421 modified "2023-10-16" @default.
• W4281781421 title "Investigating the Genetic Characteristics of Hippocampal Volume and Plasma β-Amyloid in a Chinese Community-Dwelling Population" @default.
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• W4281781421 doi "https://doi.org/10.1212/wnl.0000000000200554" @default.
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