Sex-stratified genome-wide meta-analysis identifies novel loci for cognitive decline in older adults

被引：0

作者：

Acharya, Vibha ^{[1
]}

Fan, Kang-Hsien ^{[1
]}

Snitz, Beth E. ^{[2
]}

Ganguli, Mary ^{[2
,3
,4
]}

Dekosky, Steven T. ^{[5
,6
]}

Lopez, Oscar L. ^{[2
]}

Feingold, Eleanor ^{[1
]}

Kamboh, M. Ilyas ^{[1
,3
,4
]}

机构：

[1] Univ Pittsburgh, Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA USA

[2] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA USA

[3] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA

[4] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA

[5] Univ Florida, McKnight Brain Inst, Coll Med, Gainesville, FL USA

[6] Univ Florida, Coll Med, Dept Neurol, Gainesville, FL USA

来源：

ALZHEIMERS & DEMENTIA | 2025年 / 21卷 / 03期

基金：

美国国家卫生研究院;

关键词：

cognitive decline; females; males; NDUFA12; neurocognitive domains; sex-stratified genome-wide association; GENE-EXPRESSION; OXIDATIVE-PHOSPHORYLATION; ALZHEIMER-DISEASE; DEMENTIA; ASSOCIATION; IMPAIRMENT; RISK;

D O I：

10.1002/alz.14461

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

INTRODUCTION Many complex traits and diseases show sex-specific biases in clinical presentation and prevalence. METHODS To understand sex-specific genetic architecture of cognitive decline across five cognitive domains (attention, memory, executive function, language, and visuospatial function) and global cognitive function, we performed sex-stratified genome-wide meta-analysis in 3021 older adults aged >= 65 years (female = 1545, male = 1476) from three prospective cohorts. Gene-based and gene-set enrichment analyses were conducted for each cognitive trait. RESULTS We identified a novel genome-wide significant (GWS) intergenic locus for decline of memory in males near RPS23P3 on chromosome 4 (rs6851574: minor allele frequency [MAF] = 0.39, P-male = 4.10E-08, beta(male) = 0.19; P-interaction = 3.76E-04). We also identified a subthreshold GWS locus for decline of executive function on chromosome 12 in females near the NDUFA12 gene, involved in oxidative phosphorylation (rs11107823: MAF = 0.12, P-female = 9.35E-08, beta(female) = 0.28; P-interaction = 7.42E-06). DISCUSSION Sex-aware genetic studies can help in the identification of novel genetic loci and enhance sex-specific understanding of cognitive decline.

引用

页数：14

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