Transcriptome-wide association implicates HTRA1-AS1 in age-related macular degeneration risk

Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment and legal blindness that has significant genetic risk factors, including genetic variation within a locus on chromosome 10 encompassing several extensively studied protein-coding genes (ARMS2, HTRA1 and PLEKHA1). Here, through transcriptome-wide association and fine-mapping approaches that integrate newly available high coverage transcriptome datasets for the human eye, we provide robust statistical association between elevated AMD-risk and genetic regulation of a long non-coding RNA gene within the chromosome 10 locus, HTRA1-AS1. Our findings show that increased expression of HTRA1-AS1 elevates AMD-risk and provides a new paradigm for the study of biological drivers of AMD-risk and early disease pathogenesis.