Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene

N. I. Chowdhury; A. K. Tiwari; R. P. Souza; C. C. Zai; S. A. Shaikh; S. Chen; F. Liu; J. A. Lieberman; H. Y. Meltzer; A. K. Malhotra; J. L. Kennedy; D. J. Müller

doi:10.1038/tpj.2011.66

Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene

N. I. Chowdhury, A. K. Tiwari, R. P. Souza, C. C. Zai, S. A. Shaikh, S. Chen, F. Liu, J. A. Lieberman, H. Y. Meltzer, A. K. Malhotra, J. L. Kennedy, D. J. Müller^*

^*Corresponding author for this work

Psychiatry and Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (r 2 ≤0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (P=0.027, n=69). These observations were marginal after correction for multiple testing. We performed in vitro electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings.

Original language	English (US)
Pages (from-to)	272-279
Number of pages	8
Journal	Pharmacogenomics Journal
Volume	13
Issue number	3
DOIs	https://doi.org/10.1038/tpj.2011.66
State	Published - Jun 2013

Keywords

Association study
MC4R
clozapine
electrophoretic mobility-shift assays
pharmacogenetics
weight gain

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/tpj.2011.66

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@article{5977b4da868f404da2670dd1dc7e7936,

title = "Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene",

abstract = "Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (r 2 ≤0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (P=0.027, n=69). These observations were marginal after correction for multiple testing. We performed in vitro electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings.",

keywords = "Association study, MC4R, clozapine, electrophoretic mobility-shift assays, pharmacogenetics, weight gain",

author = "Chowdhury, {N. I.} and Tiwari, {A. K.} and Souza, {R. P.} and Zai, {C. C.} and Shaikh, {S. A.} and S. Chen and F. Liu and Lieberman, {J. A.} and Meltzer, {H. Y.} and Malhotra, {A. K.} and Kennedy, {J. L.} and M{\"u}ller, {D. J.}",

note = "Funding Information: This study was supported by Canadian Institutes of Health Research (CIHR) operating grants to JLK: Strategies for Gene Discovery in Schizophrenia, MOP 15007, and Neurodevelopmental Genetics of Human Psychiatric Disorders, 200508GMH; CIHR operating grant to DJM (Genetics of antipsychotic-induced metabolic syndrome, MOP 89853); National Alliance for Research in Schizophrenia and Depression (NARSAD) Young Investigator Award; a CIHR Michael Smith New Investigator Salary Prize for Research in Schizophrenia; and an OMHF New Investigator Fellowship to DJM; MH41468, Funding from the Prentiss Foundation, Ritter Foundation, Hintz family, and the Peterson Family to HYM; Centre for Addiction and Mental Health postdoctoral fellowship to AKT; National Alliance for Research in Schizophrenia and Depression Award (NARSAD) to AKT; and CIHR fellowship XWY93967 to RPS.",

year = "2013",

month = jun,

doi = "10.1038/tpj.2011.66",

language = "English (US)",

volume = "13",

pages = "272--279",

journal = "Pharmacogenomics Journal",

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T1 - Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene

AU - Chowdhury, N. I.

AU - Tiwari, A. K.

AU - Souza, R. P.

AU - Zai, C. C.

AU - Shaikh, S. A.

AU - Chen, S.

AU - Liu, F.

AU - Lieberman, J. A.

AU - Meltzer, H. Y.

AU - Malhotra, A. K.

AU - Kennedy, J. L.

AU - Müller, D. J.

N1 - Funding Information: This study was supported by Canadian Institutes of Health Research (CIHR) operating grants to JLK: Strategies for Gene Discovery in Schizophrenia, MOP 15007, and Neurodevelopmental Genetics of Human Psychiatric Disorders, 200508GMH; CIHR operating grant to DJM (Genetics of antipsychotic-induced metabolic syndrome, MOP 89853); National Alliance for Research in Schizophrenia and Depression (NARSAD) Young Investigator Award; a CIHR Michael Smith New Investigator Salary Prize for Research in Schizophrenia; and an OMHF New Investigator Fellowship to DJM; MH41468, Funding from the Prentiss Foundation, Ritter Foundation, Hintz family, and the Peterson Family to HYM; Centre for Addiction and Mental Health postdoctoral fellowship to AKT; National Alliance for Research in Schizophrenia and Depression Award (NARSAD) to AKT; and CIHR fellowship XWY93967 to RPS.

PY - 2013/6

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N2 - Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (r 2 ≤0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (P=0.027, n=69). These observations were marginal after correction for multiple testing. We performed in vitro electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings.

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Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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