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Hum Mol Genet. 2018 Dec 7. doi: 10.1093/hmg/ddy422. [Epub ahead of print]

Genome-wide association analyses identify 139 loci associated with macular thickness in the UK Biobank cohort.

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Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.


The macula, located near the center of the retina in the human eye, is responsible for providing critical functions, such as central, sharp vision. Structural changes in the macula are associated with many ocular diseases, including age-related macular degeneration (AMD) and glaucoma. Although macular thickness is a highly heritable trait, there are no prior reported genome-wide association studies (GWASs) of it. Here, we describe the first GWAS of macular thickness, which was measured by spectral-domain optical coherence tomography using 68,423 participants from the UK Biobank cohort. We identified 139 genetic loci associated with macular thickness at genome-wide significance ($P < 5 \times 10^{-8}$). The most significant loci were LINC00461 ($P = 5.1 \times 10^{-120}$), TSPAN10 ($P = 1.2 \times 10^{-118}$), RDH5 ($P = 9.2 \times 10^{-105}$), and SLC6A20 ($P = 1.4 \times 10^{-71}$). Results from gene expression demonstrated that these genes are highly expressed in the retina. Other hits included many previously reported AMD genes, such as NPLOC4 ($P = 1.7 \times 10^{-103}$), RAD51B ($P = 9.1 \times 10^{-14}$) and SLC16A8 ($P = 1.7 \times 10^{-8}$), further providing functional significance of the identified loci. Through cross-phenotype analysis, these genetic loci also exhibited pleiotropic effects with myopia, neurodegenerative diseases (e.g. Parkinson's disease, schizophrenia, and Alzheimer's disease), cancer (e.g. breast, ovarian, and lung cancers), and metabolic traits (e.g. body mass index, waist circumference, and type 2 diabetes). Our findings provide the first insight into the genetic architecture of macular thickness and may further elucidate the pathogenesis of related ocular diseases, such as AMD.


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