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Cumulative association between age-related macular degeneration and less studied genetic variants in PLEKHA1/ARMS2/HTRA1: a meta and gene-cluster analysis

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Abstract

The objective of this study is to examine the cumulative effect of the less studied genetic variants in PLEKHA1/ARMS2/HTRA1 on age-related macular degeneration (AMD). We performed an extensive literature search for studies on the association between AMD and the less studied genetic variants in PLEKHA1/ARMS2/HTRA1. Multiple meta-analyses were performed to evaluate the association between individual genetic variants and AMD. A gene-cluster analysis was used to investigate the cumulative effect of these less studied genetic variants on AMD. A total of 23 studies from 20 published papers met the eligibility criteria and were included in our analyses. Several genetic variants in the gene cluster are significantly associated with AMD in our meta-analyses or in individual studies. Gene-cluster analysis reveals a strong cumulative association between these genetic variants in this gene cluster and AMD (p < 10−5). However, two previously suspected SNPs in ARMS2, including rs2736911, the SNP having the largest number of studies in our meta-analyses; and rs3793917, the SNP with the largest sample size, were not significantly associated with AMD (both p’s > 0.12). Sensitivity analyses reveal significant association of AMD with rs2736911 in Chinese but not in Caucasian, with c.372_815del443ins54 in Caucasian but not in Chinese, and with rs1049331 in both ethnic groups. These less studied genetic variants have a significant cumulative effect on wet AMD. Our study provides evidence of the joint contribution of genetic variants in PLEKHA1/ARMS2/HTRA1 to AMD risk, in addition to the two widely studied genetic variants whose association with AMD was well established.

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Acknowledgments

This research was supported by Award Number P50DA010075-16 from the National Institute on Drug Abuse (NIDA) and NIH/NCI R01 CA168676. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIDA or the National Institutes of Health. The sponsor or funding organization had no role in the design or conduct of this research.

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Authors and Affiliations

  1. Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China

    Weihong Yu

  2. Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Shuqian Dong

  3. Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Chuntao Zhao

  4. College of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China

    Haina Wang

  5. Division of Gastroenterology, Second Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, China

    Fei Dai

  6. The Methodology Center, Pennsylvania State University, 204 E. Calder Way, Suite 400, State College, University Park, PA, 16801, USA

    Jingyun Yang

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Correspondence to Weihong Yu or Jingyun Yang.

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Weihong Yu and Shuqian Dong contributed equally to this paper.

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Yu, W., Dong, S., Zhao, C. et al. Cumulative association between age-related macular degeneration and less studied genetic variants in PLEKHA1/ARMS2/HTRA1: a meta and gene-cluster analysis. Mol Biol Rep 40, 5551–5561 (2013). https://doi.org/10.1007/s11033-013-2656-6

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