Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population
IMPORTANCE There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is...
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| creator | Choong, Eva Quteineh, Lina Cardinaux, Jean-René Gholam-Rezaee, Mehdi Vandenberghe, Frederik Dobrinas, Maria Bondolfi, Guido Etter, Manuela Holzer, Laurent Magistretti, Pierre von Gunten, Armin Preisig, Martin Vollenweider, Peter Beckmann, Jacques S Pralong, François P Waeber, Gerard Kutalik, Zoltan Conus, Philippe Bochud, Murielle Eap, Chin B |
| description | IMPORTANCE There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown. OBJECTIVE To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population. DESIGN, SETTING, AND PARTICIPANTS Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain–inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123 865). INTERVENTION Noninterventional studies. MAIN OUTCOME AND MEASURE Difference in BMI and/or fat mass between CRTC1 genotype groups. RESULTS Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (Padjusted = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain–inducing drugs, G allele carriers (n = 98) had a 1.81–kg/m2 lower BMI than noncarriers (n = 226; P |
| doi_str_mv | 10.1001/jamapsychiatry.2013.187 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_527712</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><ama_id>1725658</ama_id><sourcerecordid>3094147241</sourcerecordid><originalsourceid>FETCH-LOGICAL-a428t-a0ab1108374958e17bc0b99842cc4fc340b2dc9708d3fe904206efacc914b44e3</originalsourceid><addsrcrecordid>eNpd0V2L1DAUBuAiirus-we80IAI3nTMV5v0ch1214EVB1nBu5Cmp0zHNKlJi_bfb8bOzqK5STg85yThzbK3BK8IxuTjXvd6iLPZdXoM84piwlZEimfZOSWlzEvK5PPTmf44yy5j3OO0JMacyZfZGWUVLQRl59m8ca2dwBlAvkXrb_drgrbezr0Pw66LfUTeoU--mdEXHSPauAb-IO0adKPHpdQ5tH18TGfQVo8duDH-ReMO0C04CNqiq2ayY5o9TDYR715lL1ptI1we94vs-831_fpzfvf1drO-uss1p3LMNdY1IVgywatCAhG1wXVVSU6N4a1hHNe0MZXAsmEtVJhTXEKrjakIrzkHdpHly9z4G4apVkPoeh1m5XWnjqWf6QSqoEIQmvyHxQ_B_5ogjqrvogFrtQM_RUU4Z6wSVXmg7_6jez8Fl35zUJgXjBQsKbEoE3yMAdrTEwhWh0DVv4GqQ6AqBZo63xznT3UPzanvMb4E3h-BjkbbNmhnuvjkhMRFiYvkXi8uXfR0u6BFWUj2AMVAtag</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1440453153</pqid></control><display><type>article</type><title>Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population</title><source>MEDLINE</source><source>American Medical Association Journals</source><source>SWEPUB Freely available online</source><creator>Choong, Eva ; Quteineh, Lina ; Cardinaux, Jean-René ; Gholam-Rezaee, Mehdi ; Vandenberghe, Frederik ; Dobrinas, Maria ; Bondolfi, Guido ; Etter, Manuela ; Holzer, Laurent ; Magistretti, Pierre ; von Gunten, Armin ; Preisig, Martin ; Vollenweider, Peter ; Beckmann, Jacques S ; Pralong, François P ; Waeber, Gerard ; Kutalik, Zoltan ; Conus, Philippe ; Bochud, Murielle ; Eap, Chin B</creator><creatorcontrib>Choong, Eva ; Quteineh, Lina ; Cardinaux, Jean-René ; Gholam-Rezaee, Mehdi ; Vandenberghe, Frederik ; Dobrinas, Maria ; Bondolfi, Guido ; Etter, Manuela ; Holzer, Laurent ; Magistretti, Pierre ; von Gunten, Armin ; Preisig, Martin ; Vollenweider, Peter ; Beckmann, Jacques S ; Pralong, François P ; Waeber, Gerard ; Kutalik, Zoltan ; Conus, Philippe ; Bochud, Murielle ; Eap, Chin B ; ODEX team</creatorcontrib><description>IMPORTANCE There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown. OBJECTIVE To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population. DESIGN, SETTING, AND PARTICIPANTS Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain–inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123 865). INTERVENTION Noninterventional studies. MAIN OUTCOME AND MEASURE Difference in BMI and/or fat mass between CRTC1 genotype groups. RESULTS Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (Padjusted = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain–inducing drugs, G allele carriers (n = 98) had a 1.81–kg/m2 lower BMI than noncarriers (n = 226; P < .0001). The strongest association was observed in women younger than 45 years, with a 3.87–kg/m2 lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001), explaining 9% of BMI variance. In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r2 = 0.7) was associated with lower BMI (sample 5, n = 123 865; P = .01) and fat mass (sample 4, n = 5338; P = .03). The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02). CONCLUSIONS AND RELEVANCE These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.</description><identifier>ISSN: 2168-622X</identifier><identifier>EISSN: 2168-6238</identifier><identifier>DOI: 10.1001/jamapsychiatry.2013.187</identifier><identifier>PMID: 23925723</identifier><language>eng</language><publisher>Chicago, IL: American Medical Association</publisher><subject>Adiposity - genetics ; Adult ; Biological and medical sciences ; Body Mass Index ; Case-Control Studies ; Female ; General aspects ; Genetic Predisposition to Disease - genetics ; Genetics ; Humans ; Male ; Medical sciences ; Mental Disorders - complications ; Mental Disorders - genetics ; Obesity ; Obesity - complications ; Obesity - genetics ; Polymorphism ; Polymorphism, Single Nucleotide ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychopharmacology ; Psychotropic drugs ; Transcription Factors - genetics</subject><ispartof>JAMA PSYCHIATRY, 2013-10, Vol.70 (10), p.1011-1019</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright American Medical Association Oct 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a428t-a0ab1108374958e17bc0b99842cc4fc340b2dc9708d3fe904206efacc914b44e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jamapsychiatry/articlepdf/10.1001/jamapsychiatry.2013.187$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jamapsychiatry/fullarticle/10.1001/jamapsychiatry.2013.187$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,550,776,780,881,3327,27901,27902,76231,76234</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27805605$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23925723$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:127490366$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Choong, Eva</creatorcontrib><creatorcontrib>Quteineh, Lina</creatorcontrib><creatorcontrib>Cardinaux, Jean-René</creatorcontrib><creatorcontrib>Gholam-Rezaee, Mehdi</creatorcontrib><creatorcontrib>Vandenberghe, Frederik</creatorcontrib><creatorcontrib>Dobrinas, Maria</creatorcontrib><creatorcontrib>Bondolfi, Guido</creatorcontrib><creatorcontrib>Etter, Manuela</creatorcontrib><creatorcontrib>Holzer, Laurent</creatorcontrib><creatorcontrib>Magistretti, Pierre</creatorcontrib><creatorcontrib>von Gunten, Armin</creatorcontrib><creatorcontrib>Preisig, Martin</creatorcontrib><creatorcontrib>Vollenweider, Peter</creatorcontrib><creatorcontrib>Beckmann, Jacques S</creatorcontrib><creatorcontrib>Pralong, François P</creatorcontrib><creatorcontrib>Waeber, Gerard</creatorcontrib><creatorcontrib>Kutalik, Zoltan</creatorcontrib><creatorcontrib>Conus, Philippe</creatorcontrib><creatorcontrib>Bochud, Murielle</creatorcontrib><creatorcontrib>Eap, Chin B</creatorcontrib><creatorcontrib>ODEX team</creatorcontrib><title>Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population</title><title>JAMA PSYCHIATRY</title><addtitle>JAMA Psychiatry</addtitle><description>IMPORTANCE There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown. OBJECTIVE To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population. DESIGN, SETTING, AND PARTICIPANTS Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain–inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123 865). INTERVENTION Noninterventional studies. MAIN OUTCOME AND MEASURE Difference in BMI and/or fat mass between CRTC1 genotype groups. RESULTS Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (Padjusted = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain–inducing drugs, G allele carriers (n = 98) had a 1.81–kg/m2 lower BMI than noncarriers (n = 226; P < .0001). The strongest association was observed in women younger than 45 years, with a 3.87–kg/m2 lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001), explaining 9% of BMI variance. In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r2 = 0.7) was associated with lower BMI (sample 5, n = 123 865; P = .01) and fat mass (sample 4, n = 5338; P = .03). The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02). CONCLUSIONS AND RELEVANCE These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.</description><subject>Adiposity - genetics</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Body Mass Index</subject><subject>Case-Control Studies</subject><subject>Female</subject><subject>General aspects</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mental Disorders - complications</subject><subject>Mental Disorders - genetics</subject><subject>Obesity</subject><subject>Obesity - complications</subject><subject>Obesity - genetics</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Psychotropic drugs</subject><subject>Transcription Factors - genetics</subject><issn>2168-622X</issn><issn>2168-6238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNpd0V2L1DAUBuAiirus-we80IAI3nTMV5v0ch1214EVB1nBu5Cmp0zHNKlJi_bfb8bOzqK5STg85yThzbK3BK8IxuTjXvd6iLPZdXoM84piwlZEimfZOSWlzEvK5PPTmf44yy5j3OO0JMacyZfZGWUVLQRl59m8ca2dwBlAvkXrb_drgrbezr0Pw66LfUTeoU--mdEXHSPauAb-IO0adKPHpdQ5tH18TGfQVo8duDH-ReMO0C04CNqiq2ayY5o9TDYR715lL1ptI1we94vs-831_fpzfvf1drO-uss1p3LMNdY1IVgywatCAhG1wXVVSU6N4a1hHNe0MZXAsmEtVJhTXEKrjakIrzkHdpHly9z4G4apVkPoeh1m5XWnjqWf6QSqoEIQmvyHxQ_B_5ogjqrvogFrtQM_RUU4Z6wSVXmg7_6jez8Fl35zUJgXjBQsKbEoE3yMAdrTEwhWh0DVv4GqQ6AqBZo63xznT3UPzanvMb4E3h-BjkbbNmhnuvjkhMRFiYvkXi8uXfR0u6BFWUj2AMVAtag</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Choong, Eva</creator><creator>Quteineh, Lina</creator><creator>Cardinaux, Jean-René</creator><creator>Gholam-Rezaee, Mehdi</creator><creator>Vandenberghe, Frederik</creator><creator>Dobrinas, Maria</creator><creator>Bondolfi, Guido</creator><creator>Etter, Manuela</creator><creator>Holzer, Laurent</creator><creator>Magistretti, Pierre</creator><creator>von Gunten, Armin</creator><creator>Preisig, Martin</creator><creator>Vollenweider, Peter</creator><creator>Beckmann, Jacques S</creator><creator>Pralong, François P</creator><creator>Waeber, Gerard</creator><creator>Kutalik, Zoltan</creator><creator>Conus, Philippe</creator><creator>Bochud, Murielle</creator><creator>Eap, Chin B</creator><general>American Medical Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20131001</creationdate><title>Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population</title><author>Choong, Eva ; Quteineh, Lina ; Cardinaux, Jean-René ; Gholam-Rezaee, Mehdi ; Vandenberghe, Frederik ; Dobrinas, Maria ; Bondolfi, Guido ; Etter, Manuela ; Holzer, Laurent ; Magistretti, Pierre ; von Gunten, Armin ; Preisig, Martin ; Vollenweider, Peter ; Beckmann, Jacques S ; Pralong, François P ; Waeber, Gerard ; Kutalik, Zoltan ; Conus, Philippe ; Bochud, Murielle ; Eap, Chin B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a428t-a0ab1108374958e17bc0b99842cc4fc340b2dc9708d3fe904206efacc914b44e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adiposity - genetics</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Body Mass Index</topic><topic>Case-Control Studies</topic><topic>Female</topic><topic>General aspects</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mental Disorders - complications</topic><topic>Mental Disorders - genetics</topic><topic>Obesity</topic><topic>Obesity - complications</topic><topic>Obesity - genetics</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Psychotropic drugs</topic><topic>Transcription Factors - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choong, Eva</creatorcontrib><creatorcontrib>Quteineh, Lina</creatorcontrib><creatorcontrib>Cardinaux, Jean-René</creatorcontrib><creatorcontrib>Gholam-Rezaee, Mehdi</creatorcontrib><creatorcontrib>Vandenberghe, Frederik</creatorcontrib><creatorcontrib>Dobrinas, Maria</creatorcontrib><creatorcontrib>Bondolfi, Guido</creatorcontrib><creatorcontrib>Etter, Manuela</creatorcontrib><creatorcontrib>Holzer, Laurent</creatorcontrib><creatorcontrib>Magistretti, Pierre</creatorcontrib><creatorcontrib>von Gunten, Armin</creatorcontrib><creatorcontrib>Preisig, Martin</creatorcontrib><creatorcontrib>Vollenweider, Peter</creatorcontrib><creatorcontrib>Beckmann, Jacques S</creatorcontrib><creatorcontrib>Pralong, François P</creatorcontrib><creatorcontrib>Waeber, Gerard</creatorcontrib><creatorcontrib>Kutalik, Zoltan</creatorcontrib><creatorcontrib>Conus, Philippe</creatorcontrib><creatorcontrib>Bochud, Murielle</creatorcontrib><creatorcontrib>Eap, Chin B</creatorcontrib><creatorcontrib>ODEX team</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>JAMA PSYCHIATRY</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choong, Eva</au><au>Quteineh, Lina</au><au>Cardinaux, Jean-René</au><au>Gholam-Rezaee, Mehdi</au><au>Vandenberghe, Frederik</au><au>Dobrinas, Maria</au><au>Bondolfi, Guido</au><au>Etter, Manuela</au><au>Holzer, Laurent</au><au>Magistretti, Pierre</au><au>von Gunten, Armin</au><au>Preisig, Martin</au><au>Vollenweider, Peter</au><au>Beckmann, Jacques S</au><au>Pralong, François P</au><au>Waeber, Gerard</au><au>Kutalik, Zoltan</au><au>Conus, Philippe</au><au>Bochud, Murielle</au><au>Eap, Chin B</au><aucorp>ODEX team</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population</atitle><jtitle>JAMA PSYCHIATRY</jtitle><addtitle>JAMA Psychiatry</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>70</volume><issue>10</issue><spage>1011</spage><epage>1019</epage><pages>1011-1019</pages><issn>2168-622X</issn><eissn>2168-6238</eissn><abstract>IMPORTANCE There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown. OBJECTIVE To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population. DESIGN, SETTING, AND PARTICIPANTS Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain–inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123 865). INTERVENTION Noninterventional studies. MAIN OUTCOME AND MEASURE Difference in BMI and/or fat mass between CRTC1 genotype groups. RESULTS Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (Padjusted = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain–inducing drugs, G allele carriers (n = 98) had a 1.81–kg/m2 lower BMI than noncarriers (n = 226; P < .0001). The strongest association was observed in women younger than 45 years, with a 3.87–kg/m2 lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001), explaining 9% of BMI variance. In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r2 = 0.7) was associated with lower BMI (sample 5, n = 123 865; P = .01) and fat mass (sample 4, n = 5338; P = .03). The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02). CONCLUSIONS AND RELEVANCE These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.</abstract><cop>Chicago, IL</cop><pub>American Medical Association</pub><pmid>23925723</pmid><doi>10.1001/jamapsychiatry.2013.187</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | JAMA PSYCHIATRY, 2013-10, Vol.70 (10), p.1011-1019 |
| issn | 2168-622X 2168-6238 |
| language | eng |
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| source | MEDLINE; American Medical Association Journals; SWEPUB Freely available online |
| subjects | Adiposity - genetics Adult Biological and medical sciences Body Mass Index Case-Control Studies Female General aspects Genetic Predisposition to Disease - genetics Genetics Humans Male Medical sciences Mental Disorders - complications Mental Disorders - genetics Obesity Obesity - complications Obesity - genetics Polymorphism Polymorphism, Single Nucleotide Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychopharmacology Psychotropic drugs Transcription Factors - genetics |
| title | Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T19%3A19%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Influence%20of%20CRTC1%20Polymorphisms%20on%20Body%20Mass%20Index%20and%20Fat%20Mass%20in%20Psychiatric%20Patients%20and%20the%20General%20Adult%20Population&rft.jtitle=JAMA%20PSYCHIATRY&rft.au=Choong,%20Eva&rft.aucorp=ODEX%20team&rft.date=2013-10-01&rft.volume=70&rft.issue=10&rft.spage=1011&rft.epage=1019&rft.pages=1011-1019&rft.issn=2168-622X&rft.eissn=2168-6238&rft_id=info:doi/10.1001/jamapsychiatry.2013.187&rft_dat=%3Cproquest_swepu%3E3094147241%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1440453153&rft_id=info:pmid/23925723&rft_ama_id=1725658&rfr_iscdi=true |