@article {1598031,
	title = {Gene Set Enrichment Analsyes Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy},
	journal = {Am J Ophthalmol},
	volume = {233},
	year = {2022},
	month = {2022 01},
	pages = {111-123},
	abstract = {To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses applied to genome-wide association study meta-analyses. METHODS: We analyzed DR GWAS meta-analyses performed on 3246 Europeans and 2611 African Americans with type 2 diabetes. Gene sets relevant to 5 key DR pathophysiology processes were investigated: tissue injury, vascular events, metabolic events and glial dysregulation, neuronal dysfunction, and inflammation. Keywords relevant to these processes were queried in 4 pathway and ontology databases. Two GSEA methods, Meta-Analysis Gene set Enrichment of variaNT Associations (MAGENTA) and Multi-marker Analysis of GenoMic Annotation (MAGMA), were used. Gene sets were defined to be enriched for gene associations with DR if the P value corrected for multiple testing (Pcorr) was \&lt;.05. RESULTS: Five gene sets were significantly enriched for numerous modest genetic associations with DR in one method (MAGENTA or MAGMA) and also at least nominally significant (uncorrected P \&lt; .05) in the other method. These pathways were regulation of the lipid catabolic process (2-fold enrichment, Pcorr\&nbsp;=\&nbsp;.014); nitric oxide biosynthesis (1.92-fold enrichment, Pcorr\&nbsp;=\&nbsp;.022); lipid digestion, mobilization, and transport (1.6-fold enrichment, P\&nbsp;=\&nbsp;.032); apoptosis (1.53-fold enrichment, P\&nbsp;=\&nbsp;.041); and retinal ganglion cell degeneration (2-fold enrichment, Pcorr\&nbsp;=\&nbsp;.049). The interferon gamma (IFNG) gene, previously implicated in DR by protein-protein interactions in our GWAS, was among the top ranked genes in the nitric oxide pathway (best variant P\&nbsp;=\&nbsp;.0001). CONCLUSIONS: These GSEA indicate that variants in genes involved in oxidative stress, lipid transport and catabolism, and cell degeneration are enriched for genes associated with DR risk. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.},
	keywords = {Diabetes Mellitus, Type 2, Diabetic Retinopathy, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk Factors},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2021.06.014},
	author = {Sobrin, Lucia and Susarla, Gayatri and Stanwyck, Lynn and Rouhana, John M and Li, Ashley and Pollack, Samuela and Igo, Robert P and Jensen, Richard A and Li, Xiaohui and Ng, Maggie C Y and Smith, Albert V and Kuo, Jane Z and Taylor, Kent D and Freedman, Barry I and Bowden, Donald W and Penman, Alan and Chen, Ching J and Craig, Jamie E and Adler, Sharon G and Chew, Emily Y and Cotch, Mary Frances and Yaspan, Brian and Mitchell, Paul and Wang, Jie Jin and Klein, Barbara E K and Wong, Tien Y and Rotter, Jerome I and Burdon, Kathyrn P and Iyengar, Sudha K and Segr{\`e}, Ayellet V}
}
