Grunin, Michelle and Triffon, Daria and Beykin, Gala and Rahmani, Elior and Schweiger, Regev and Tiosano, Liran and Khateb, Samer and Hagbi-Levi, Shira and Rinsky, Batya and Munitz, Refael and Winkler, Thomas W. and Heid, Iris M. and Halperin, Eran and Carmi, Shai and Chowers, Itay (2024) Genome wide association study and genomic risk prediction of age related macular degeneration in Israel. SCIENTIFIC REPORTS, 14 (1): 13034. ISSN 2045-2322
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The risk of developing age-related macular degeneration (AMD) is influenced by genetic background. In 2016, the International AMD Genomics Consortium (IAMDGC) identified 52 risk variants in 34 loci, and a polygenic risk score (PRS) from these variants was associated with AMD. The Israeli population has a unique genetic composition: Ashkenazi Jewish (AJ), Jewish non-Ashkenazi, and Arab sub-populations. We aimed to perform a genome-wide association study (GWAS) for AMD in Israel, and to evaluate PRSs for AMD. Our discovery set recruited 403 AMD patients and 256 controls at Hadassah Medical Center. We genotyped individuals via custom exome chip. We imputed non-typed variants using cosmopolitan and AJ reference panels. We recruited additional 155 cases and 69 controls for validation. To evaluate predictive power of PRSs for AMD, we used IAMDGC summary-statistics excluding our study and developed PRSs via clumping/thresholding or LDpred2. In our discovery set, 31/34 loci reported by IAMDGC were AMD-associated (P < 0.05). Of those, all effects were directionally consistent with IAMDGC and 11 loci had a P-value under Bonferroni-corrected threshold (0.05/34 = 0.0015). At a 5 x 10(-5) threshold, we discovered four suggestive associations in FAM189A1, IGDCC4, C7orf50, and CNTNAP4. Only the FAM189A1 variant was AMD-associated in the replication cohort after Bonferroni-correction. A prediction model including LDpred2-based PRS + covariates had an AUC of 0.82 (95% CI 0.79-0.85) and performed better than covariates-only model (P = 5.1 x 10(-9)). Therefore, previously reported AMD-associated loci were nominally associated with AMD in Israel. A PRS developed based on a large international study is predictive in Israeli populations.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POLYGENIC RISK; SCORES; POLYMORPHISM; INCREASES; PHENOTYPE; GENETICS; FAMILY |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jan 2026 06:54 |
| Last Modified: | 28 Jan 2026 06:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65260 |
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