title: Extremely discordant sib-pair study design to determine risk factors for neovascular age-related macular degeneration.
abstract: OBJECTIVE
  To search for factors that contribute to the development of neovascular age-related macular degeneration (AMD).
  
  
  METHODS
  In a matched-pair case-control study, we studied sib pairs in which the index sibling had neovascular AMD in at least 1 eye and the unaffected sibling had normal maculae (or at most only a few small drusen) and was past the age at which the index case was diagnosed. Factors studied included sex, iris color, education, alcohol consumption, body mass index, vitamin use, smoking history, hypercholesterolemia, aspirin use, hypertension, other cardiovascular disease, any autoimmune disease, and non-insulin-dependent diabetes mellitus. Conditional logistic regression was performed to identify predictors of neovascular AMD.
  
  
  RESULTS
  On the basis of 73 sib pairs, multivariate regression analysis revealed a statistically significant 2% increase in risk of neovascular AMD with each pack-year of smoking (odds ratio, 1.02; 95% confidence interval, 1.01-1.04; P =.007). Suggestive but nonsignificant associations were also observed for mean lifetime alcohol consumption, adult lifetime body mass index, and hypertension in multivariate regression analyses.
  
  
  CONCLUSIONS
  Using extremely discordant sib pairs to study risk factors for AMD, a novel approach in epidemiological design, we found evidence that smoking is a risk factor for neovascular AMD.
authors.affiliation: Ocular Molecular Genetics Institute, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: DeAngelis
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Lane
authors.forename: Chirag P
authors.initials: CP
authors.lastname: Shah
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.forename: Thaddeus P
authors.initials: TP
authors.lastname: Dryja
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects; D001327:Autoimmune Diseases / Q000150:complications; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000150:complications; D020256:Choroidal Neovascularization / Q000453:epidemiology* / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004522:Educational Status; D015340:Epidemiologic Research Design; D005127:Eye Color; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D012307:Risk Factors; D012737:Sex Factors; D035781:Siblings; D012907:Smoking / Q000009:adverse effects; D014815:Vitamins / Q000008:administration & dosage
chemical_list: D014815:Vitamins