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

E J Brandl; A K Tiwari; C C Zai; E L Nurmi; N I Chowdhury; T Arenovich; M Sanches; V F Goncalves; J J Shen; J A Lieberman; H Y Meltzer; J L Kennedy; D J Müller

doi:10.1038/tpj.2015.59

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

Pharmacogenomics J. 2016 Aug;16(4):352-6. doi: 10.1038/tpj.2015.59. Epub 2015 Sep 1.

Authors

E J Brandl^{1

2}, A K Tiwari¹, C C Zai^{1

3}, E L Nurmi⁴, N I Chowdhury¹, T Arenovich¹, M Sanches¹, V F Goncalves^{1

3}, J J Shen⁵, J A Lieberman⁶, H Y Meltzer⁷, J L Kennedy^{1

3}, D J Müller^{1

3}

Affiliations

¹ Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
² Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
³ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁴ Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Semel Institute for Neuroscience, Los Angeles, CA, USA.
⁵ Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China.
⁶ Department of Psychiatry, College of Physicians and Surgeons, Columbia University and the New York State Psychiatric Institute, New York City, NY, USA.
⁷ Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, IL, USA.

PMID: 26323598
DOI: 10.1038/tpj.2015.59

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.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.59.

Publication types

Meta-Analysis
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antipsychotic Agents / adverse effects*
Carrier Proteins / genetics
Europe
Female
Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged
Pharmacogenomic Testing
Pharmacogenomic Variants / drug effects*
Phenotype
Polymorphism, Single Nucleotide*
Randomized Controlled Trials as Topic
Risk Assessment
Risk Factors
Schizophrenia / drug therapy*
United States
Weight Gain / drug effects*
Weight Gain / genetics*

Substances

Antipsychotic Agents
Carrier Proteins
IBA57 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding