title: Accounting for relatedness in family based genetic association studies.
abstract: OBJECTIVE
  Assess the differences in point estimates, power and type 1 error rates when accounting for and ignoring family structure in genetic tests of association.
  
  
  METHODS
  We compare by simulation the performance of analytic models using variance components to account for family structure and regression models that ignore relatedness for a range of possible family based study designs (i.e., sib pairs vs. large sibships vs. nuclear families vs. extended families).
  
  
  RESULTS
  Our analyses indicate that effect size estimates and power are not significantly affected by ignoring family structure. Type 1 error rates increase when family structure is ignored, as density of family structures increases, and as trait heritability increases. For discrete traits with moderate levels of heritability and across many common sampling designs, type 1 error rates rise from a nominal 0.05 to 0.11.
  
  
  CONCLUSIONS
  Ignoring family structure may be useful in screening although it comes at a cost of a increased type 1 error rate, the magnitude of which depends on trait heritability and pedigree configuration.
authors.affiliation: Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. pmcardle@epi.umaryland.edu
authors.forename: P F
authors.initials: PF
authors.lastname: McArdle
authors.forename: J R
authors.initials: JR
authors.lastname: O'Connell
authors.forename: T I
authors.initials: TI
authors.lastname: Pollin
authors.forename: M
authors.initials: M
authors.lastname: Baumgarten
authors.forename: A R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: P A
authors.initials: PA
authors.lastname: Peyser
authors.forename: B D
authors.initials: BD
authors.lastname: Mitchell
mesh_terms: D005190:Family; D008040:Genetic Linkage; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008957:Models, Genetic; D010375:Pedigree; D012044:Regression Analysis