title: Assessing susceptibility to age-related macular degeneration with genetic markers and environmental factors.
abstract: OBJECTIVE
  To evaluate the independent and joint effects of genetic factors and environmental variables on advanced forms of age-related macular degeneration (AMD), including geographic atrophy and choroidal neovascularization, and to develop a predictive model with genetic and environmental factors included.
  
  
  METHODS
  Demographic information, including age at onset, smoking status, and body mass index, was collected for 1844 participants. Genotypes were evaluated for 8 variants in 5 genes related to AMD. Unconditional logistic regression analyses were performed to generate a risk predictive model.
  
  
  RESULTS
  All genetic variants showed a strong association with AMD. Multivariate odds ratios were 3.52 (95% confidence interval, 2.08-5.94) for complement factor H, CFH rs1061170 CC, 4.21 (2.30-7.70) for CFH rs2274700 CC, 0.46 (0.27-0.80) for C2 rs9332739 CC/CG, 0.44 (0.30-0.66) for CFB rs641153 TT/CT, 10.99 (6.04-19.97) for HTRA1/LOC387715 rs10490924 TT, and 2.66 (1.43-4.96) for C3 rs2230199 GG. Smoking was independently associated with advanced AMD after controlling for age, sex, body mass index, and all genetic variants.
  
  
  CONCLUSIONS
  CFH confers more risk to the bilaterality of geographic atrophy, whereas HTRA1/LOC387715 contributes more to the bilaterality of choroidal neovascularization. C3 confers more risk for geographic atrophy than choroidal neovascularization. Risk models with combined genetic and environmental factors have notable discrimination power.
  
  
  CONCLUSIONS
  Early detection and risk prediction of AMD could help to improve the prognosis of AMD and to reduce the outcome of blindness. Targeting high-risk individuals for surveillance and clinical interventions may help reduce disease burden.
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California, San Diego, USA.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Jiexi
authors.initials: J
authors.lastname: Zeng
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.forename: Kevin
authors.initials: K
authors.lastname: Wang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trood
authors.forename: Jeanette
authors.initials: J
authors.lastname: Buehler
authors.forename: Matthew
authors.initials: M
authors.lastname: Weed
authors.forename: Daniel
authors.initials: D
authors.lastname: Kasuga
authors.forename: Paul S
authors.initials: PS
authors.lastname: Bernstein
authors.forename: Guy
authors.initials: G
authors.lastname: Hughes
authors.forename: Victoria
authors.initials: V
authors.lastname: Fu
authors.forename: Jessica
authors.initials: J
authors.lastname: Chin
authors.forename: Clara
authors.initials: C
authors.lastname: Lee
authors.forename: Maureen
authors.initials: M
authors.lastname: Crocker
authors.forename: Matthew
authors.initials: M
authors.lastname: Bedell
authors.forename: Francesca
authors.initials: F
authors.lastname: Salasar
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.forename: Michael
authors.initials: M
authors.lastname: Goldbaum
authors.forename: Henry
authors.initials: H
authors.lastname: Ferreyra
authors.forename: William R
authors.initials: WR
authors.lastname: Freeman
authors.forename: Igor
authors.initials: I
authors.lastname: Kozak
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000235:genetics*; D003176:Complement C3 / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D057092:Geographic Atrophy / Q000175:diagnosis / Q000235:genetics*; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D016015:Logistic Models; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D056186:Metagenomics; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D012907:Smoking
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; D003176:Complement C3; D005819:Genetic Markers; D011506:Proteins; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases