Hierarchical Classes Analysis (HICLAS): A novel data reduction method to examine associations between biallelic SNPs and perceptual organization phenotypes in schizophrenia.
The power of SNP association studies to detect valid relationships with clinical phenotypes in schizophrenia is largely limited by the number of SNPs selected and non-specificity of phenotypes. To address this, we first assessed performance on two visual perceptual organization tasks designed to avoid many generalized deficit confounds, Kanizsa shape perception and contour integration, in a schizophrenia patient sample. Then, to reduce the total number of candidate SNPs analyzed in association with perceptual organization phenotypes, we employed a two-stage strategy: firsta prioriSNPs from three candidate genes were selected (GAD1, NRG1 and DTNBP1); then a Hierarchical Classes Analysis (HICLAS) was performed to reduce the total number of SNPs, based on statistically related SNP clusters. HICLAS reduced the total number of candidate SNPs for subsequent phenotype association analyses from 6 to 3. MANCOVAs indicated that rs10503929 and rs1978340 were associated with the Kanizsa shape perceptionfilling inmetric but not theglobal shapedetection metric. rs10503929 was also associated with altered contour integration performance. SNPs not selected by the HICLAS model were unrelated to perceptual phenotype indices. While the contribution of candidate SNPs to perceptual impairments requires further clarification, this study reports the first application of HICLAS as a hypothesis-independent mathematical method for SNP data reduction. HICLAS may be useful for future larger scale genotype-phenotype association studies.
Rutgers University Graduate School of Biomedical Sciences, 675 Hoes Lane, Piscataway, NJ 08854, USA ; Rutgers University Behavioral Health Care, 151 Centennial Ave, Piscataway, NJ 08854, USA.
Jamie
J
Joseph
Rutgers University Behavioral Health Care, 151 Centennial Ave, Piscataway, NJ 08854, USA ; Rutgers-Robert Wood Johnson Medical School, 671 Hoes Lane, Piscataway, NJ 08854, USA.
Michael A
MA
Gara
Rutgers University Behavioral Health Care, 151 Centennial Ave, Piscataway, NJ 08854, USA ; Rutgers-Robert Wood Johnson Medical School, 671 Hoes Lane, Piscataway, NJ 08854, USA.
Steven M
SM
Silverstein
Data reduction; Hierarchical Classes Analysis (HICLAS); Perceptual organization phenotypes; SNP; Schizophrenia