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

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作者
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
机构
[1] Pharmacogenetics Research Clinic,Department of Psychiatry and Psychotherapy
[2] Campbell Family Mental Health Research Institute,Department of Psychiatry
[3] Centre for Addiction and Mental Health,Department of Psychiatry and Biobehavioral Sciences
[4] Charité Universitätsmedizin Berlin,Department of Pediatrics and Adolescent Medicine
[5] University of Toronto,Department of Psychiatry
[6] University of California at Los Angeles,Department of Psychiatry and Behavioral Sciences
[7] Semel Institute for Neuroscience,undefined
[8] The University of Hong Kong,undefined
[9] College of Physicians and Surgeons,undefined
[10] Columbia University and the New York State Psychiatric Institute,undefined
[11] Northwestern Feinberg School of Medicine,undefined
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摘要
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.
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页码:352 / 356
页数:4
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