title: On family-based genome-wide association studies with large pedigrees: observations and recommendations.
abstract: Family based association studies are employed less often than case-control designs in the search for disease-predisposing genes. The optimal statistical genetic approach for complex pedigrees is unclear when evaluating both common and rare variants. We examined the empirical power and type I error rates of 2 common approaches, the measured genotype approach and family-based association testing, through simulations from a set of multigenerational pedigrees. Overall, these results suggest that much larger sample sizes will be required for family-based studies and that power was better using MGA compared to FBAT. Taking into account computational time and potential bias, a 2-step strategy is recommended with FBAT followed by MGA.
authors.affiliation: Department of Biostatistics, University of Kentucky College of Public Health, 111 Washington Ave, Lexington, KY 40536, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Fardo
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA ; Department of Pediatrics, University of Cincinnati College of Medicine, 2600 Clifton Ave, Cincinnati, OH 45229, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA ; Department of Pediatrics, University of Cincinnati College of Medicine, 2600 Clifton Ave, Cincinnati, OH 45229, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Kurowski
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, 2600 Clifton Ave, Cincinnati, OH 45229, USA.
authors.forename: Eileen S
authors.initials: ES
authors.lastname: Alexander
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA ; Department of Pediatrics, University of Cincinnati College of Medicine, 2600 Clifton Ave, Cincinnati, OH 45229, USA.
authors.forename: Tesfaye B
authors.initials: TB
authors.lastname: Mersha
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pilipenko
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Kottyan
authors.affiliation: Department of Biostatistics, University of Kentucky College of Public Health, 111 Washington Ave, Lexington, KY 40536, USA.
authors.forename: Kannabiran
authors.initials: K
authors.lastname: Nandakumar
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA ; Department of Pediatrics, University of Cincinnati College of Medicine, 2600 Clifton Ave, Cincinnati, OH 45229, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Martin