Age-related macular degeneration (AMD) is the leading cause worldwide of severe visual impairment among people older than 55 years of age. This study aimed to investigate the genetic association between coding and untranslated region (UTR) variants in previously reported loci and exudative age-related macular degeneration (wet AMD) in a Han Chinese population. Using our previously published whole exome sequencing dataset of 349 wet AMD patients and 1253 controls, we searched for associations between coding and UTR variants of the 72 genes located within the 47 reported wet AMD loci regions. From these, 25 variants in 18 of the 72 genes with P < 10 × 10−3 were selected for the first replication of Sequenom mass-array genotyping in 885 wet AMD subjects and 562 controls. Next, four SNPs were selected for further validation by SNaPshot genotyping in a third Chinese cohort with 456 wet AMD subjects and 211 controls. As a result, we identified two new potential coding and UTR variant SNPs (rs189132250 in BBX located in 3q12.1 and rs144351944 in FILIP1L located in 3q12.1) that showed weak associations with wet AMD in the Han Chinese population. These findings provide new information regarding the coding and UTR variants of the known wet AMD loci in the studied Chinese cohort.
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We would like to thank all the AMD patients and their families for participating in this study. This research project was supported by: National key scientific research program (2016YFC0905200, ZY), the National Natural Science Foundation of China (81170883(ZY), 81430008 (ZY), 81470647(FW), 81300802 and 81670895 (LH), the Department of Science and Technology of Sichuan Province, China (2014SZ0169 (ZY), 2015SZ0052 (ZY), 2015JQO057 (LH), 2013JY0195 (LH), 2016HH0072(LH), and 2017JQ0024(LH).
ZY designed the study. FW, XZ, POST, HC and CP recruited the participants. LH and FH performed the genotyping. LH wrote the initial draft, with edits from ZY corrected the English spelling and grammar. All authors critically revised and gave final approval of this manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
The URLs for data presented herein are as follows: 1000 Genomes Browser, http://browser.1000genomes.org/index.html; GWAS Integrator database (https://phgkb.cdc.gov/HuGENavigator/gWAHitStartPage.do); UCSC hg19:http://genome.ucsc.edu/; BWA: http://bio-bwa.sourceforge.net/; SAMTOOLS: http://samtools.sourceforge.net/; Annovar: http://annovar.openbioinformatics.org/en/latest/.