title: A novel method for testing association of multiple genetic markers with a multinomial trait.
abstract: We developed a multinomial probit model with singular value decomposition for testing a large number of single nucleotide polymorphisms (SNPs) simultaneously, using maximum likelihood estimation and permutation. The method was validated by simulation. We simulated 1000 SNPs, including 9 associated with disease states, and 8 of the 9 were successfully identified. Applying the method to study 32 genes in our Mexican-American samples for association with prediabetes through either impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), we found 3 genes (SORCS1, AMPD1, PPAR) associated with both IGT and IFG, while 5 genes (AMPD2, PRKAA2, C5, TCF7L2, ITR) with the IGT mechanism only and 6 genes (CAPN10, IL4,NOS3, CD14, GCG, SORT1) with the IFG mechanism only. These data suggest that IGT and IFG may indicate different physiological mechanism to prediabetes, via different genetic determinants.
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Soonil
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Jinrui
authors.initials: J
authors.lastname: Cui
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Y-D Ida
authors.initials: YD
authors.lastname: Chen
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: The Methodist Hospital Research Institute, Houston, TX.
authors.forename: Willa
authors.initials: W
authors.lastname: Hsueh
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo