MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.

The overall goal of this supplement project is to expand the scientific activities that were funded in the parent grant (PI: Pasquale, "Gene-Environment Interactions in Glaucoma", Grant EY015473). The specific aims of the parent grant were to 1) identify cases of primary open-angle glaucoma (POAG) in two ongoing large prospective studies (the Nurses' Health Study [NHS] and Health Professionals Follow-up Study [HPFS]) and 2) conduct association studies in relation to POAG of environmental risk factors such as menopausal status and alcohol, NOS3, which is a candidate gene for POAG, and the interactions between NOS3 and environmental factors. We have made significant progress on the aims of the parent grant. We have identified nearly 1100 cases of POAG in the two cohorts (800 cases with DNA). In addition, we have been able to procure additional funding to conduct a genome wide association study (GWAS) of POAG (PI: Pasquale, "Genes and Environment Initiative in Glaucoma", Grant U01 HG004728-01) where we will utilize the DNA from the identified cases and controls in the parent study. We are in the process of conducting the nested case-control studies of NOS3 and NOS3 and environment interactions in relation to POAG and are planning for the replication phase of the GWAS; both efforts will require increases in case numbers for optimal power. We have the opportunity at low cost to increase the sample size of our study for evaluating gene-environment interaction studies; thus, we request a supplement with one specific aim: to identify additional incident cases and controls in two prospective studies (Women's Health Study [WHS] and Physician's Health Study [PHS]), which have collected information on various environmental factors as well as DNA in a subset of participants. Using the same validated method of case-identification that we used in the parent study, we project that we will be able to identify 700 additional cases from these two studies (480 with existing high throughput genome wide scan data), which will greatly increase the power for the aims of the parent grant, and will allow for replication of the findings from the newly funded GWAS. The analyses using the data from confirmed cases and matched controls will be conducted using funds and resources from the parent study. This supplement will thus accelerate scientific research and will also involve hiring a full-time project coordinator to oversee the case identification of POAG in the two cohorts; thus, this supplement is in compliance with the objectives of the Recovery Act.

Clarification of Codes