Genome-wide screen to identify genetic loci associated with cognitive decline in late-life depression.
Genome-wide screen to identify genetic loci associated with cognitive decline in late-life depression.
复制标题
全基因组筛查，以确定与晚年抑郁症认知能力下降相关的遗传位点。
DOI：
10.1017/s1041610220001143
复制
发表时间：
2020-07-09
影响因子：
7
通讯作者：
Potter GG
中科院分区：
文献类型：
--
作者：
Steffens DC;Garrett ME;Soldano KL;McQuoid DR;Ashley-Koch AE;Potter GG
This study sought to conduct a comprehensive search for genetic risk of cognitive decline in the context of geriatric depression. A genomewide association study (GWAS) analysis in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study. Longitudinal, naturalistic follow-up study Older depressed adults, both outpatients and inpatients, receiving care at an academic medical center. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery was administered to the study participants at baseline and a minimum of twice within a subsequent three-year period in order to measure cognitive decline. A GWAS analysis was conducted to identify genetic variation that is associated with baseline and change in the CERAD Total Score (CERAD-TS) in NCODE. The GWAS of baseline CERAD-TS revealed a significant association with an intergenic SNP on chromosome 6, rs17662598, that surpassed adjustment for multiple testing (p=3.7x10-7, FDR q=0.0371). For each additional G allele, average baseline CERAD-TS decreased by 8.656 points. The most significant SNP that lies within a gene was rs11666579 in SLC27A1 (p=1.1x10-5). Each additional copy of the G allele was associated with an average decrease of baseline CERAD-TS of 4.829 points. SLC27A1 is involved with processing docosahexaenoic acid (DHA), an endogenous neuroprotective compound in the brain. Decreased levels of DHA have been associated with the development of Alzheimer’s disease (AD). The most significant SNP associated with CERAD-TS decline over time was rs73240021 in GRXCR1 (p=1.1x10-6), a gene previously linked with deafness. However, none of the associations within genes survived adjustment for multiple testing. Our GWAS of cognitive function and decline among individuals with LLD has identified promising candidate genes that, upon replication in other cohorts of LLD, may be potential biomarkers for cognitive decline and suggests DHA supplementation as a possible therapy of interest.
