Genome-wide association study on antipsychotic-induced weight gain in the CATIE sample.
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.
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
E J
EJ
Brandl
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
A K
AK
Tiwari
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
C C
CC
Zai
Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Semel Institute for Neuroscience, Los Angeles, CA, USA.
E L
EL
Nurmi
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
N I
NI
Chowdhury
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
T
T
Arenovich
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
M
M
Sanches
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
V F
VF
Goncalves
Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China.
J J
JJ
Shen
Department of Psychiatry, College of Physicians and Surgeons, Columbia University and the New York State Psychiatric Institute, New York City, NY, USA.
J A
JA
Lieberman
Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, IL, USA.
H Y
HY
Meltzer
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
J L
JL
Kennedy
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
D J
DJ
Müller
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D002352:Carrier Proteins / Q000235:genetics; D005060:Europe; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants / Q000187:drug effects*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy*; D014481:United States; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics*
D014150:Antipsychotic Agents; D002352:Carrier Proteins; C585465:IBA57 protein, human