A Validated Phenotyping Algorithm for Genetic Association Studies in Age-related Macular Degeneration

作者：Simonett Joseph M; Sohrab Mahsa A; Pacheco Jennifer; Armstrong Loren L; Rzhetskaya Margarita; Smith Maureen; Hayes M Geoffrey; Fawzi Amani A^*

来源：Scientific Reports, 2015, 5(1): 12875.

DOI：10.1038/srep12875

Age-related macular degeneration (AMD), a multifactorial, neurodegenerative disease, is a leading cause of vision loss. With the rapid advancement of DNA sequencing technologies, many AMD-associated genetic polymorphisms have been identified. Currently, the most time consuming steps of these studies are patient recruitment and phenotyping. In this study, we describe the development of an automated algorithm to identify neovascular (wet) AMD, non-neovascular (dry) AMD and control subjects using electronic medical record (EMR)-based criteria. Positive predictive value (91.7%) and negative predictive value (97.5%) were calculated using expert chart review as the gold standard to assess algorithm performance. We applied the algorithm to an EMR-linked DNA bio-repository to study previously identified AMD-associated single nucleotide polymorphisms (SNPs), using case/control status determined by the algorithm. Risk alleles of three SNPs, rs1061170 (CFH), rs1410996 (CFH), and rs10490924 (ARMS2) were found to be significantly associated with the AMD case/control status as defined by the algorithm. With the rapid growth of EMR-linked DNA biorepositories, patient selection algorithms can greatly increase the efficiency of genetic association study. We have found that stepwise validation of such an algorithm can result in reliable cohort selection and, when coupled within an EMR-linked DNA biorepository, replicates previously published AMD-associated SNPs.

• 出版日期2015-8-10
• 单位西北大学