TY - JOUR
T1 - Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration
AU - Ratnapriya, Rinki
AU - Sosina, Olukayode A.
AU - Starostik, Margaret R.
AU - Kwicklis, Madeline
AU - Kapphahn, Rebecca J.
AU - Fritsche, Lars G.
AU - Walton, Ashley
AU - Arvanitis, Marios
AU - Gieser, Linn
AU - Pietraszkiewicz, Alexandra
AU - Montezuma, Sandra R.
AU - Chew, Emily Y.
AU - Battle, Alexis
AU - Abecasis, Gonçalo R.
AU - Ferrington, Deborah A.
AU - Chatterjee, Nilanjan
AU - Swaroop, Anand
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41588-019-0351-9
DO - 10.1038/s41588-019-0351-9
M3 - Letter
C2 - 30742112
AN - SCOPUS:85061356250
SN - 1061-4036
VL - 51
SP - 606
EP - 610
JO - Nature genetics
JF - Nature genetics
IS - 4
ER -