ArticleEBioMedicine2026
A multi-ancestry genome-wide association study of dry eye disease and systemic comorbidities.
Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundDry eye disease (DED) affects up to 25% of the adult population, with chronic symptoms of pain and dryness often negatively impacting quality of life. Twin studies indicate a substantial heritability. However, the genetic architecture of DED is largely unknown.
methodsWe devised a case-control algorithm using a combination of ICD-9/10 codes and prescription records and validated its performance through manual chart review, identifying 132,637 DED cases and 352,201 controls across four ancestry groups in the Million Veteran Program biobank. We then performed multi-ancestry genome-wide and phenome-wide association scans. A replication analysis was performed in the Genetic Epidemiology Research on Adult Health and Aging biobank (up to 16,025 cases and 54,818 controls). Genetic correlations were assessed using linkage disequilibrium score regression and multivariate relationships were modelled using genomic structural equation modelling (genomicSEM).
findingsWe identify ten significant loci in nine susceptibility regions with largely consistent effects across ancestries, including loci linked to synapse maintenance (EFNA5, GRIA1, and SYNGAP1) and autoimmunity (BLK). Phenome-wide scans for genetic pleiotropy indicate substantial genetic correlations of DED with numerous comorbidities, including fibromyalgia (r
interpretationThe observed genetic correlations are consistent with shared genetic liability between DED and chronic pain, autoimmune, and psychiatric traits, but do not establish causal direction.
fundingThis work was supported by the US Department of Veterans Affairs, the Department of Defense, the National Eye Institute/NIH, and Research to Prevent Blindness. Full funding details are provided in the Acknowledgements.
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