Molecular pathway analysis associates alterations in obesity related genes and antipsychotic-induced weight gain

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Molecular pathway analysis associates alterations in obesity related genes and antipsychotic-induced weight gain. / Corfitsen, Henrik Thyge; Krantz, Betina; Larsen, Agnete; Drago, Antonio.

I: Acta Neuropsychiatrica, Bind 32, Nr. 2, 2020, s. 72-83.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{831ed29f56bd4779b492aa47938d6990,
title = "Molecular pathway analysis associates alterations in obesity related genes and antipsychotic-induced weight gain",
abstract = "OBJECTIVE: Antipsychotics often induce excessive weight gain. We hypothesized that individuals with genetic variations related to known obesity-risk genes have an increased risk of excessive antipsychotic-induced weight gain. This hypothesis was tested in a subset of the CATIE trial data-set.METHODS: The CATIE trial compared effects and side effects of five different antipsychotics through an 18 month period. Based on the maximum weight gain recorded, excessive weight gain was defined as >7% weight-gain. Cytoscape and GeneMania were instrumental in composing a molecular pathway from eight selected genes linked to obesity. Genetic information on a total of 495.172 SNPs were available from 765 (556 males) individuals. Enrichment test was conducted through reactomePA and Bioconductor. A permutation test was performed, testing the generated pathway against 105 permutated pathways (pRESULT: GWAS analysis did not detect significant differences related to excessive weight gain. The pathway generated contained 28 genes. A total of 2067 SNPs were significantly expressed (p<0.01) within this pathway when comparing excessive weight gainers to the rest of the sample. Affected genes included PPARG and PCSK1 not previously related to treatment-induced weight gain.CONCLUSIONS: The molecular pathway composed from high-risk obesity genes, was shown to overlap with genetics of patients who gained > 7% weight gain during the CATIE trial. This suggests that genes related to obesity, composes a pathway of increased risk of excessive antipsychotic-induced weight gain. Further independent analyses are warranted that may confirm or clarify the possible reasoning behind.",
keywords = "Antipsychotic Agents, Keywords:, Metabolic Networks and Pathways, Pharmacogenetics, Polymorphism, Single Nucleotide, Weight Gain",
author = "Corfitsen, {Henrik Thyge} and Betina Krantz and Agnete Larsen and Antonio Drago",
year = "2020",
doi = "10.1017/neu.2019.41",
language = "English",
volume = "32",
pages = "72--83",
journal = "Acta Neuropsychiatrica",
issn = "0924-2708",
publisher = "Cambridge University Press",
number = "2",

}

RIS

TY - JOUR

T1 - Molecular pathway analysis associates alterations in obesity related genes and antipsychotic-induced weight gain

AU - Corfitsen, Henrik Thyge

AU - Krantz, Betina

AU - Larsen, Agnete

AU - Drago, Antonio

PY - 2020

Y1 - 2020

N2 - OBJECTIVE: Antipsychotics often induce excessive weight gain. We hypothesized that individuals with genetic variations related to known obesity-risk genes have an increased risk of excessive antipsychotic-induced weight gain. This hypothesis was tested in a subset of the CATIE trial data-set.METHODS: The CATIE trial compared effects and side effects of five different antipsychotics through an 18 month period. Based on the maximum weight gain recorded, excessive weight gain was defined as >7% weight-gain. Cytoscape and GeneMania were instrumental in composing a molecular pathway from eight selected genes linked to obesity. Genetic information on a total of 495.172 SNPs were available from 765 (556 males) individuals. Enrichment test was conducted through reactomePA and Bioconductor. A permutation test was performed, testing the generated pathway against 105 permutated pathways (pRESULT: GWAS analysis did not detect significant differences related to excessive weight gain. The pathway generated contained 28 genes. A total of 2067 SNPs were significantly expressed (p<0.01) within this pathway when comparing excessive weight gainers to the rest of the sample. Affected genes included PPARG and PCSK1 not previously related to treatment-induced weight gain.CONCLUSIONS: The molecular pathway composed from high-risk obesity genes, was shown to overlap with genetics of patients who gained > 7% weight gain during the CATIE trial. This suggests that genes related to obesity, composes a pathway of increased risk of excessive antipsychotic-induced weight gain. Further independent analyses are warranted that may confirm or clarify the possible reasoning behind.

AB - OBJECTIVE: Antipsychotics often induce excessive weight gain. We hypothesized that individuals with genetic variations related to known obesity-risk genes have an increased risk of excessive antipsychotic-induced weight gain. This hypothesis was tested in a subset of the CATIE trial data-set.METHODS: The CATIE trial compared effects and side effects of five different antipsychotics through an 18 month period. Based on the maximum weight gain recorded, excessive weight gain was defined as >7% weight-gain. Cytoscape and GeneMania were instrumental in composing a molecular pathway from eight selected genes linked to obesity. Genetic information on a total of 495.172 SNPs were available from 765 (556 males) individuals. Enrichment test was conducted through reactomePA and Bioconductor. A permutation test was performed, testing the generated pathway against 105 permutated pathways (pRESULT: GWAS analysis did not detect significant differences related to excessive weight gain. The pathway generated contained 28 genes. A total of 2067 SNPs were significantly expressed (p<0.01) within this pathway when comparing excessive weight gainers to the rest of the sample. Affected genes included PPARG and PCSK1 not previously related to treatment-induced weight gain.CONCLUSIONS: The molecular pathway composed from high-risk obesity genes, was shown to overlap with genetics of patients who gained > 7% weight gain during the CATIE trial. This suggests that genes related to obesity, composes a pathway of increased risk of excessive antipsychotic-induced weight gain. Further independent analyses are warranted that may confirm or clarify the possible reasoning behind.

KW - Antipsychotic Agents

KW - Keywords:

KW - Metabolic Networks and Pathways

KW - Pharmacogenetics

KW - Polymorphism, Single Nucleotide

KW - Weight Gain

U2 - 10.1017/neu.2019.41

DO - 10.1017/neu.2019.41

M3 - Journal article

C2 - 31619305

VL - 32

SP - 72

EP - 83

JO - Acta Neuropsychiatrica

JF - Acta Neuropsychiatrica

SN - 0924-2708

IS - 2

ER -