Retinal Transcriptome-Wide Association Study Identifies Novel Alzheimer's Disease Risk Genes

INTRODUCTION: Alzheimer's disease (AD) is the leading cause of dementia worldwide. The retina shares molecular pathways with the brain, yet no study has systematically linked retinal gene expression to AD risk. METHODS: We performed transcriptome-wide association studies (TWAS) using two independent retinal eQTL panels (Strunz et al., n = 311; EyeGEx, n = 406) and a large meta-analyzed AD genome-wide association study (GWAS) (Bellenguez et al., 111,326 cases, 677,663 controls). Genes were further validated with GWAS in the independent Alzheimer's Disease Sequencing Project (ADSP) using a matched eQTL-panel strategy. RESULTS: We identified 62 AD-associated genes across the two eQTL panels usi