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

Area of Science:

• Pharmacogenomics
• Genetics
• Psychiatry

Background:

• Antipsychotic-induced weight gain (AIWG) is a frequent and significant adverse effect of antipsychotic medications.
• A substantial portion of AIWG susceptibility is attributed to genetic factors.
• Identifying genetic markers for AIWG is crucial for personalized treatment strategies.

Purpose of the Study:

• To reanalyze genome-wide association study (GWAS) data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) cohort.
• To identify novel genetic variants associated with antipsychotic-induced weight gain (AIWG).
• To validate potential findings in an independent patient cohort.

Main Methods:

• Reanalysis of existing GWAS data from the CATIE study using a refined patient subset (N=189).
• Genome-wide association analysis to identify single-nucleotide polymorphisms (SNPs) associated with AIWG.
• Replication analysis of top candidate SNPs in an independent cohort (N=86).
• Meta-analysis combining results from both cohorts.

Main Results:

• No SNPs reached genome-wide significance (P < 5x10(-8)) in the initial analysis.
• Several SNPs, including rs9346455 (upstream of OGFRL1), showed suggestive association.
• The SNP rs9346455 demonstrated significant association with AIWG in the replication cohort (P=0.005).
• Combined meta-analysis yielded a significant P-value for rs9346455 (P=1.09x10(-7)).

Conclusions:

• The reanalysis of the CATIE GWAS data suggests novel genetic variants, particularly rs9346455, are associated with AIWG.
• These findings highlight the potential for genetic markers to predict or explain AIWG.
• Further research is required to elucidate the functional mechanisms of these identified polymorphisms.