RT Journal Article
SR Electronic
T1 Towards the identification of causal genes for age-related macular degeneration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 778613
DO 10.1101/778613
A1 Cheng, Fei-Fei
A1 Zhuang, You-Yuan
A1 Wen, Xin-Ran
A1 Xue, Angli
A1 Yang, Jian
A1 Jin, Zi-Bing
YR 2019
UL http://biorxiv.org/content/early/2019/09/23/778613.abstract
AB Age-related macular degeneration (AMD) is a leading cause of visual impairment in ageing populations and has no radical treatment or prevention. Although genome-wide association studies (GWAS) have identified many susceptibility loci for AMD, the underlying causal genes remain elusive. Here, we prioritized nine putative causal genes by integrating expression quantitative trait locus (eQTL) data from blood (n = 2,765) with AMD GWAS data (16,144 cases vs. 17,832 controls) and replicated six of them using retina eQTL data (n = 523). Of the six genes, altering expression of cnn2, sarm1 and bloc1s1 led to ocular phenotype, impaired vision and retinal pigment epithelium (RPE) loss in zebrafish. Essential photoreceptor and RPE genes were downregulated in cnn2- and sarm1-knockdown zebrafishes. Through integration of GWAS and eQTL data followed by functional validation, our study reveals potential roles of CNN2, SARM1 and BLOC1S1 in AMD pathogenesis and demonstrates an efficient platform to prioritise causal genes for human complex diseases.