Genome-wide association study on antipsychotic-induced weight gain in the CATIE sample

Abstract

Antipsychotic-induced weight gain (AIWG) is a common side effect with a high genetic contribution. We reanalyzed genome-wide association study (GWAS) data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) selecting a refined subset of patients most suitable for AIWG studies. The final GWAS was conducted in N=189 individuals. The top polymorphisms were analyzed in a second cohort of N=86 patients. None of the single-nucleotide polymorphisms was significant at the genome-wide threshold of 5x10 -8. We observed interesting trends for rs9346455 (P=6.49x10 -6) upstream of OGFRL1, the intergenic variants rs7336345 (P=1.31 × 10 -5) and rs1012650 (P=1.47 × 10 -5), and rs1059778 (P=1.49x10 -5) in IBA57. In the second cohort, rs9346455 showed significant association with AIWG (P=0.005). The combined meta-analysis P-value for rs9346455 was 1.09 × 10 -7. Our reanalysis of the CATIE GWAS data revealed interesting new variants associated with AIWG. As the functional relevance of these polymorphisms is yet to be determined, further studies are needed.