Using ancestry matching to combine family-based and unrelated samples for genome-wide association studies

作者：Crossett Andrew; Kent Brian P; Klei Lambertus; Ringquist Steven; Trucco Massimo; Roeder Kathryn^*; Devlin Bernie

来源：Statistics in Medicine, 2010, 29(28): 2932-2945.

DOI：10.1002/sim.4057

• conditional logistic regression
• family based design
• genome wide association
• matched case-control
• population stratification

We propose a method to analyze family based samples together with unrelated cases and controls The method builds on the idea of matched case-Control analysis using conditional logistic regression (CLR) For each trio within the family a case (the proband) and matched pseudo controls are constructed, based upon the transmitted and untransmitted alleles Unrelated controls matched by genetic ancestry supplement the sample of pseudo controls, likewise unrelated cases are also paired with genetically matched controls Within each matched stratum, the case genotype is contrasted with control/pseudo control genotypes via CLR, using a method we call matched CLR (mCLR) Eigenanalysis of numerous SNP genotypes provides a tool for mapping genetic ancestry The result of such an analysis can be thought of as a multidimensional map, or eigenmap, in which the relative genetic similarities and differences amongst individuals is encoded in the map Once constructed new individuals can be projected onto the ancestry map based on their genotypes Successful differentiation of individuals of distinct ancestry depends on having a diverse, yet representative sample from which to con

• 出版日期2010-12-10