title: Genetic determinants of age-related macular degeneration in diverse populations from the PAGE study.
abstract: OBJECTIVE
  Substantial progress has been made in identifying susceptibility variants for AMD in European populations; however, few studies have been conducted to understand the role these variants play in AMD risk in diverse populations. The present study aims to examine AMD risk across diverse populations in known and suspected AMD complement factor and lipid-related loci.
  
  
  METHODS
  Targeted genotyping was performed across study sites for AMD and lipid trait-associated single nucleotide polymorphism (SNPs). Genetic association tests were performed at individual sites and then meta-analyzed using logistic regression assuming an additive genetic model stratified by self-described race/ethnicity. Participants included cases with early or late AMD and controls with no signs of AMD as determined by fundus photography. Populations included in this study were European Americans, African Americans, Mexican Americans, and Singaporeans from the Population Architecture using Genomics and Epidemiology (PAGE) study.
  
  
  RESULTS
  Index variants of AMD, rs1061170 (CFH) and rs10490924 (ARMS2), were associated with AMD at P=3.05×10(-8) and P=6.36×10(-6), respectively, in European Americans. In general, none of the major AMD index variants generalized to our non-European populations with the exception of rs10490924 in Mexican Americans at an uncorrected P value<0.05. Four lipid-associated SNPS (LPL rs328, TRIB1 rs6987702, CETP rs1800775, and KCTD10/MVK rs2338104) were associated with AMD in African Americans and Mexican Americans (P<0.05), but these associations did not survive strict corrections for multiple testing.
  
  
  CONCLUSIONS
  While most associations did not generalize in the non-European populations, variants within lipid-related genes were found to be associated with AMD. This study highlights the need for larger well-powered studies in non-European populations.
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Restrepo
authors.affiliation: Department of Biology and Environmental Science, Heidelberg University, Tiffin, Ohio, United States.
authors.forename: Kylee L
authors.initials: KL
authors.lastname: Spencer
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Goodloe
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
authors.forename: Tiana A
authors.initials: TA
authors.lastname: Garrett
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington, United States.
authors.forename: Petra
authors.initials: P
authors.lastname: Bůžková
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington, United States.
authors.forename: Neal
authors.initials: N
authors.lastname: Jorgensen
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Jensen
authors.affiliation: Department of Genetics, Rutgers University, Piscataway, New Jersey, United States.
authors.forename: Tara C
authors.initials: TC
authors.lastname: Matise
authors.affiliation: Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Hindorff
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore.
authors.forename: Tien Y
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Belinda K
authors.initials: BK
authors.lastname: Cornes
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.affiliation: Center for Systems Genomics, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, United States.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; D011506:Proteins; D017242:Complement Factor H; D004247:DNA
keywords: ARMS2 A69S; CFH Y402H; PAGE Study; age-related macular degeneration; genetic epidemiology