Genome-Wide Association Study of Age-Related Macular Degeneration Reveals 2 New Loci Implying Shared Genetic Components with Central Serous Chorioretinopathy.
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Akiyama Masato, Miyake Masahiro, Momozawa Yukihide, Arakawa Satoshi, Maruyama-Inoue Maiko, Endo Mikiko, Iwasaki Yusuke, Ishigaki Kazuyoshi, Matoba Nana, Okada Yukinori, Yasuda Miho, Oshima Yuji, Yoshida Shigeo, Nakao Shin-Ya, Morino Kazuya, Mori Yuki, Kido Ai, Kato Aki, Yasukawa Tsutomu, Obata Ryo, Nagai Yoshimi, Takahashi Kanji, Fujisawa Kimihiko, Miki Akiko, Nakamura Makoto, Honda Shigeru, Ushida Hiroaki, Yasuma Tetsuhiro, Nishiguchi Koji M, Mori Ryusaburo, Tanaka Koji, Wakatsuki Yu, Yamashiro Kenji, Kadonosono Kazuaki, Terao Chikashi, Ishibashi Tatsuro, Tsujikawa Akitaka, Sonoda Koh-Hei, Kubo Michiaki, Kamatani Yoichiro
Аннотация
DESIGN: Genome-wide association study (GWAS).
PARTICIPANTS: Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses.
METHODS: We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants.
MAIN OUTCOME MEASURES: Associations of genetic variants with AMD.
RESULTS: A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P < 5.0 × 10-8). Of these loci, 4 were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2), and 2 were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all datasets, we observed strong associations in these loci (P = 1.88 × 10-12 and P = 1.35 × 10-9 for meta-analysis for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were associated significantly with CSC (P = 4.86 × 10-3 and P = 4.28 × 10-3 for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (rg [the measure of genetic correlation] = -0.33; P = 0.01; false discovery rate, 0.099).
CONCLUSIONS: Our findings imply shared genetic components conferring the risk of both AMD and CSC.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.