The design, execution, and interpretation of genetic association studies to decipher complex diseases

Genetic association studies are becoming increasingly frequent in the obstetric and gynecologic literature and they are considered central to the deciphering of the genetic basis of complex disease. The purpose, design, execution, analysis, and interpretation of genetic association studies in reproduction are discussed. Frequently used terms are defined (eg, genotype, haplotype, polymorphism, single nucleotide polymorphism, linkage disequilibrium). Guidelines are proposed for the evaluation of reports of genetic association studies (including selection of polymorphisms for study, study design, assay characteristics, sample size, multiple testing, and multivariable analysis). The potential value of this type of investigation in elucidating the mechanisms of disease in reproduction is illustrated.