title: Impact of home visit capacity on genetic association studies of late-onset Alzheimer's disease.
abstract: BACKGROUND
  Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.
  
  
  METHODS
  We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.
  
  
  RESULTS
  LOAD associations nominally differed for 4 of 21 variants; CR1 and APOE variants were significant after Bonferroni correction.
  
  
  CONCLUSIONS
  Estimates of genetic associations may differ for studies limited to clinic-only designs. Home visit capacity should be explored as a possible source of heterogeneity and potential bias in genetic studies.
authors.affiliation: Department of Biostatistics and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Fardo
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Gibbons
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Shubhabrata
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Epidemiology, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: M Maria
authors.initials: MM
authors.lastname: Glymour
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: McCormick
authors.affiliation: Department of Psychosocial and Community Health, University of Washington, Seattle, WA, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: McCurry
authors.affiliation: Department of Neurology, Swedish Medical Center, Seattle, WA, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Bowen
authors.affiliation: Group Health Research Institute, Group Health, Seattle, WA, USA.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Larson
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: pcrane@uw.edu.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crane
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006792:House Calls; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D011446:Prospective Studies; D017463:Receptors, Complement 3b / Q000235:genetics; D012107:Research Design; D012737:Sex Factors; D054063:Superior Sagittal Sinus
chemical_list: D001057:Apolipoproteins E; C509991:CR1 protein, human; D017463:Receptors, Complement 3b
keywords: Ascertainment bias; Bias; Cohort studies; Genetics; Genome-wide association studies; Genome-wide studies; Home research study visits; Inference; Late-onset Alzheimer's disease; Longitudinal studies; Missing data; Population-based studies; Prospective studies; Research clinic study visits; Selection bias