{"doi":"10.3390/nu8120793","title":"Polymorphism of the Transcription Factor 7-Like 2 Gene (TCF7L2) Interacts with Obesity on Type-2 Diabetes in the PREDIMED Study Emphasizing the Heterogeneity of Genetic Variants in Type-2 Diabetes Risk Prediction: Time for Obesity-Specific Genetic Risk Scores","abstract":"<jats:p>Nutrigenetic studies analyzing gene–diet interactions of the TCF7L2-rs7903146 C &gt; T polymorphism on type-2 diabetes (T2D) have shown controversial results. A reason contributing to this may be the additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C &gt; T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample. We studied 7018 PREDIMED participants at baseline and longitudinally (8.7 years maximum follow-up). Obesity significantly interacted with the TCF7L2-rs7903146 on T2D prevalence, associations being greater in non-obese subjects. Accordingly, we prospectively observed in non-T2D subjects (n = 3607) that its association with T2D incidence was stronger in non-obese (HR: 1.81; 95% CI: 1.13–2.92, p = 0.013 for TT versus CC) than in obese subjects (HR: 1.01; 95% CI: 0.61–1.66; p = 0.979; p-interaction = 0.048). Accordingly, TCF7L2-PV was higher in non-obese subjects. Additionally, we created obesity-specific GRS with ten T2D-polymorphisms and demonstrated for the first time their higher strata-specific PV. In conclusion, we provide strong evidence supporting the need for considering obesity when analyzing the TCF7L2 effects and propose the use of obesity-specific GRS for T2D.</jats:p>","journal":"Nutrients","year":2016,"id":605158,"datarank":0.62147020895873,"base_score":4.143134726391533,"endowment":4.143134726391533,"self_citation_contribution":0.62147020895873,"citation_network_contribution":0.0,"self_endowment_contribution":0.62147020895873,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":442291,"name":"Óscar Coltell","orcid":"0000-0002-4518-8495","position":1,"is_corresponding":false},{"id":84252,"name":"José V. 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A reason contributing to this may be the additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C &gt; T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample. We studied 7018 PREDIMED participants at baseline and longitudinally (8.7 years maximum follow-up). Obesity significantly interacted with the TCF7L2-rs7903146 on T2D prevalence, associations being greater in non-obese subjects. Accordingly, we prospectively observed in non-T2D subjects (n = 3607) that its association with T2D incidence was stronger in non-obese (HR: 1.81; 95% CI: 1.13–2.92, p = 0.013 for TT versus CC) than in obese subjects (HR: 1.01; 95% CI: 0.61–1.66; p = 0.979; p-interaction = 0.048). Accordingly, TCF7L2-PV was higher in non-obese subjects. Additionally, we created obesity-specific GRS with ten T2D-polymorphisms and demonstrated for the first time their higher strata-specific PV. In conclusion, we provide strong evidence supporting the need for considering obesity when analyzing the TCF7L2 effects and propose the use of obesity-specific GRS for T2D.</jats:p>","is_dataset_classified":null,"base_score":4.143134726391533,"endowment":4.143134726391533,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27929407","pmcid":"PMC5188448","openalex_id":"https://openalex.org/W2560642009","authors":[],"funders":[{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"CIBER 06/03","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"PI051839","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"PI070240","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"PI1001407","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"G03/140","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"RD06/0045","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"PI07-0954","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"CNIC-06","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"PI11/02505","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"SAF2009-12304","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"AGL2010-22319-C03-03","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"PRX14/00527","title":null},{"funder_name":"Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional","grant_id":"contract JR14/00008","title":null},{"funder_name":"University Jaume I","grant_id":"P1-1B2013-54","title":null},{"funder_name":"Generalitat Valenciana","grant_id":"AP111/10","title":null},{"funder_name":"Generalitat Valenciana","grant_id":"AP-042/11","title":null},{"funder_name":"Generalitat Valenciana","grant_id":"BEST/2015/087","title":null},{"funder_name":"Generalitat Valenciana","grant_id":"GVACOMP2011-151","title":null},{"funder_name":"Generalitat Valenciana","grant_id":"ACOMP/2011/145","title":null},{"funder_name":"Generalitat Valenciana","grant_id":"ACOMP/2012/190","title":null},{"funder_name":"Generalitat Valenciana","grant_id":"ACOMP/2013/159","title":null},{"funder_name":"U.S. Department of Agriculture - 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