Abstract Details

Title Investigating the Genetic Characteristics of Hippocampal Volume and Plasma Aß in a Chinese Community-Dwelling Population

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 023

Objective 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.

Background The genetic characteristics and correlations of hippocampal volume and plasm Aβ, probable endophenotypes for dementia, remain to be explored in Chinese community cohort.

Design/Methods Whole-exome sequencing and SNP-array genotyping were conducted among 1,261 individuals from a Chinese community cohort, and association analyses were performed for hippocampal volumes and plasm Aβ with mixed-effect linear regression models 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.

Results 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, SEM=0.017) from whole-exome sequencing and rs6030088 (P=8.24×10^-9, β=-105.22 SEM=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.

Conclusions 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.

Authors/Disclosures
Xinzhuang Yang PRESENTER	Xinzhuang Yang has nothing to disclose.
Mengyao Wan (Peking Union Medical College)	Miss Wan has nothing to disclose.

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