D C Steffens, M E Garrett, K L Soldano, D R McQuoid, A E Ashley-Koch, G G Potter
{"title":"通过全基因组筛选，确定与晚年抑郁症认知能力下降相关的基因位点。","authors":"D C Steffens, M E Garrett, K L Soldano, D R McQuoid, A E Ashley-Koch, G G Potter","doi":"10.1017/S1041610220001143","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study sought to conduct a comprehensive search for genetic risk of cognitive decline in the context of geriatric depression.</p><p><strong>Design: </strong>A genome-wide association study (GWAS) analysis in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study.</p><p><strong>Setting: </strong>Longitudinal, naturalistic follow-up study.</p><p><strong>Participants: </strong>Older depressed adults, both outpatients and inpatients, receiving care at an academic medical center.</p><p><strong>Measurements: </strong>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 3-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.</p><p><strong>Results: </strong>The GWAS of baseline CERAD-TS revealed a significant association with an intergenic single-nucleotide polymorphism (SNP) on chromosome 6, rs17662598, that surpassed adjustment for multiple testing (<i>p</i> = 3.7 × 10<sup>-7</sup>; false discovery rate <i>q</i> = 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 <i>SLC27A1</i> (<i>p</i> = 1.1 × 10<sup>-5</sup>). Each additional copy of the G allele was associated with an average decrease of baseline CERAD-TS of 4.829 points. <i>SLC27A1</i> 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. The most significant SNP associated with CERAD-TS decline over time was rs73240021 in <i>GRXCR1</i> (<i>p</i> = 1.1 × 10<sup>-6</sup>), a gene previously linked with deafness. However, none of the associations within genes survived adjustment for multiple testing.</p><p><strong>Conclusions: </strong>Our GWAS of cognitive function and decline among individuals with late-life depression (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.</p>","PeriodicalId":14368,"journal":{"name":"International psychogeriatrics","volume":" ","pages":"1021-1029"},"PeriodicalIF":4.6000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794099/pdf/nihms-1601798.pdf","citationCount":"0","resultStr":"{\"title\":\"Genome-wide screen to identify genetic loci associated with cognitive decline in late-life depression.\",\"authors\":\"D C Steffens, M E Garrett, K L Soldano, D R McQuoid, A E Ashley-Koch, G G Potter\",\"doi\":\"10.1017/S1041610220001143\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>This study sought to conduct a comprehensive search for genetic risk of cognitive decline in the context of geriatric depression.</p><p><strong>Design: </strong>A genome-wide association study (GWAS) analysis in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study.</p><p><strong>Setting: </strong>Longitudinal, naturalistic follow-up study.</p><p><strong>Participants: </strong>Older depressed adults, both outpatients and inpatients, receiving care at an academic medical center.</p><p><strong>Measurements: </strong>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 3-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.</p><p><strong>Results: </strong>The GWAS of baseline CERAD-TS revealed a significant association with an intergenic single-nucleotide polymorphism (SNP) on chromosome 6, rs17662598, that surpassed adjustment for multiple testing (<i>p</i> = 3.7 × 10<sup>-7</sup>; false discovery rate <i>q</i> = 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 <i>SLC27A1</i> (<i>p</i> = 1.1 × 10<sup>-5</sup>). Each additional copy of the G allele was associated with an average decrease of baseline CERAD-TS of 4.829 points. <i>SLC27A1</i> 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. The most significant SNP associated with CERAD-TS decline over time was rs73240021 in <i>GRXCR1</i> (<i>p</i> = 1.1 × 10<sup>-6</sup>), a gene previously linked with deafness. However, none of the associations within genes survived adjustment for multiple testing.</p><p><strong>Conclusions: </strong>Our GWAS of cognitive function and decline among individuals with late-life depression (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.</p>\",\"PeriodicalId\":14368,\"journal\":{\"name\":\"International psychogeriatrics\",\"volume\":\" \",\"pages\":\"1021-1029\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794099/pdf/nihms-1601798.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International psychogeriatrics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1017/S1041610220001143\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2020/7/9 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"GERIATRICS & GERONTOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International psychogeriatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1017/S1041610220001143","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/7/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
Participants: Older depressed adults, both outpatients and inpatients, receiving care at an academic medical center.
Measurements: 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 3-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.
Results: The GWAS of baseline CERAD-TS revealed a significant association with an intergenic single-nucleotide polymorphism (SNP) on chromosome 6, rs17662598, that surpassed adjustment for multiple testing (p = 3.7 × 10-7; false discovery rate 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 = 1.1 × 10-5). 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. The most significant SNP associated with CERAD-TS decline over time was rs73240021 in GRXCR1 (p = 1.1 × 10-6), a gene previously linked with deafness. However, none of the associations within genes survived adjustment for multiple testing.
Conclusions: Our GWAS of cognitive function and decline among individuals with late-life depression (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.
期刊介绍：
A highly respected, multidisciplinary journal, International Psychogeriatrics publishes high quality original research papers in the field of psychogeriatrics. The journal aims to be the leading peer reviewed journal dealing with all aspects of the mental health of older people throughout the world. Circulated to over 1,000 members of the International Psychogeriatric Association, International Psychogeriatrics also features important editorials, provocative debates, literature reviews, book reviews and letters to the editor.
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