现象
疾病
全基因组关联研究
联想(心理学)
遗传倾向
遗传关联
基因组
医学
生物
遗传学
单核苷酸多态性
心理学
基因型
基因
病理
心理治疗师
作者
Archita S. Khaire,Courtney E. Wimberly,Eleanor C Semmes,Jillian H. Hurst,Kyle M. Walsh
标识
DOI:10.1016/j.neurobiolaging.2022.05.011
摘要
Genome-wide association studies (GWAS) have identified common single nucleotide polymorphisms (SNPs) that increase late-onset Alzheimer's disease (LOAD) risk. To identify additional LOAD-associated variants and provide insight into underlying disease biology, we performed a phenome-wide association study on 23 known LOAD-associated SNPs and 4:1 matched control SNPs using UK Biobank data. LOAD-associated SNPs were significantly enriched for associations with 8/778 queried traits, including 3 platelet traits. The strongest enrichment was for platelet distribution width (PDW) (p = 1.2 × 10-5), but increased PDW was not associated with LOAD susceptibility in Mendelian randomization analysis. Of 384 PDW-associated SNPs identified by prior GWAS, 36 were nominally associated with LOAD risk (17,008 cases; 37,154 controls) and 5 survived false-discovery rate correction. Associations confirmed known LOAD risk loci near PICALM, CD2AP, SPI1, and NDUFAF6, and identified a novel risk locus in epidermal growth factor receptor. Integrating GWAS and phenome-wide association study data reveals substantial pleiotropy between genetic determinants of LOAD and of platelet morphology, and for the first time implicates epidermal growth factor receptor - a mediator of β-amyloid toxicity - in Alzheimer's disease susceptibility.
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