Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration

Rinki Ratnapriya, Olukayode A. Sosina, Margaret R. Starostik, Madeline Kwicklis, Rebecca J. Kapphahn, Lars G. Fritsche, Ashley Walton, Marios Arvanitis, Linn Gieser, Alexandra Pietraszkiewicz, Sandra R. Montezuma, Emily Y. Chew, Alexis Battle, Gonçalo R. Abecasis, Deborah A. Ferrington, Nilanjan Chatterjee, Anand Swaroop

Research output: Contribution to journalArticlepeer-review

158 Scopus citations


Genome-wide association studies (GWAS) have identified genetic variants at 34 loci contributing to age-related macular degeneration (AMD)1–3. We generated transcriptional profiles of postmortem retinas from 453 controls and cases at distinct stages of AMD and integrated retinal transcriptomes, covering 13,662 protein-coding and 1,462 noncoding genes, with genotypes at more than 9 million common SNPs for expression quantitative trait loci (eQTL) analysis of a tissue not included in Genotype-Tissue Expression (GTEx) and other large datasets4,5. Cis-eQTL analysis identified 10,474 genes under genetic regulation, including 4,541 eQTLs detected only in the retina. Integrated analysis of AMD-GWAS with eQTLs ascertained likely target genes at six reported loci. Using transcriptome-wide association analysis (TWAS), we identified three additional genes, RLBP1, HIC1 and PARP12, after Bonferroni correction. Our studies expand the genetic landscape of AMD and establish the Eye Genotype Expression (EyeGEx) database as a resource for post-GWAS interpretation of multifactorial ocular traits.

Original languageEnglish (US)
Pages (from-to)606-610
Number of pages5
JournalNature Genetics
Issue number4
StatePublished - Apr 1 2019

Bibliographical note

Funding Information:
The authors acknowledge B. Weber for providing liver eQTL data. We thank members of the laboratory of A.S., especially H. Yang, J. Bryan, A. Police Reddy, and F. Giuste for assistance, and the Lions Gift of Sight members for procuring human retina tissue. This work was supported by the Intramural Research Program of the National Eye Institute EY000450, EY000474, and EY000475 (to A.S.), NIH grants EY028554 and EY026012, The Lindsay Family Foundation, an anonymous benefactor, and the Minnesota Lions Vision Foundation (to D.A.F.), and the Johns Hopkins Bloomberg Distinguished Professorship Endowment (to N.C.). This study used the high-performance computational capabilities of the Biowulf Linux cluster (see URLs).

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.


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