title: Genome-wide association and admixture analysis of glaucoma in the Women's Health Initiative.
abstract: We report a genome-wide association study (GWAS) and admixture analysis of glaucoma in 12 008 African-American and Hispanic women (age 50-79 years) from the Women's Health Initiative (WHI). Although GWAS of glaucoma have been conducted on several populations, this is the first to look at glaucoma in individuals of African-American and Hispanic race/ethnicity. Prevalent and incident glaucoma was determined by self-report from study questionnaires administered at baseline (1993-1998) and annually through 2005. For African Americans, there was a total of 658 prevalent cases, 1062 incident cases and 6067 individuals who never progressed to glaucoma. For our replication cohort, we used the WHI Hispanics, including 153 prevalent cases, 336 incident cases and 2685 non-cases. We found an association of African ancestry with glaucoma incidence in African Americans (hazards ratio 1.62, 95% CI 1.023-2.56, P = 0.038) and in Hispanics (hazards ratio 3.21, 95% CI 1.32-7.80, P = 0.011). Although we found that no previously identified glaucoma SNPs replicated in either the WHI African Americans or Hispanics, a risk score combining all previously reported hits was significant in African-American prevalent cases (P = 0.0046), and was in the expected direction in the incident cases, as well as in the Hispanic incident cases. Additionally, after imputing to 1000 Genomes, two less common independent SNPs were suggestive in African Americans, but had too low of an allele frequency in Hispanics to test for replication. These results suggest the possibility of a distinct genetic architecture underlying glaucoma in individuals of African ancestry.
authors.affiliation: Department of Epidemiology and Biostatistics and Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA, hoffmannt@humgen.ucsf.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hoffmann
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Thornton
authors.affiliation: Division of Research, Kaiser Permanente, Oakland, CA 94612, USA.
authors.forename: Bette
authors.initials: B
authors.lastname: Caan
authors.affiliation: Department of Epidemiology and Biostatistics and.
authors.forename: Mary
authors.initials: M
authors.lastname: Haan
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, The State University of New York, Buffalo, NY 14214, USA and.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Millen
authors.affiliation: Department of Preventative Medicine, University of Tennessee Health Science Center, Memphis, TN 38105, USA.
authors.forename: Fridtjof
authors.initials: F
authors.lastname: Thomas
authors.affiliation: Department of Epidemiology and Biostatistics and Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA, Division of Research, Kaiser Permanente, Oakland, CA 94612, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Risch
mesh_terms: D001741:Black or African American; D000368:Aged; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005901:Glaucoma / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D006630:Hispanic or Latino; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012306:Risk; D057566:Self Report; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology; D016387:Women's Health