000121399 001__ 121399
000121399 005__ 20240319081020.0
000121399 0247_ $$2doi$$a10.1038/s41398-022-01783-7
000121399 0248_ $$2sideral$$a131897
000121399 037__ $$aART-2022-131897
000121399 041__ $$aeng
000121399 100__ $$aAnguita-Ruiz, Augusto
000121399 245__ $$aBody mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals
000121399 260__ $$c2022
000121399 5060_ $$aAccess copy available to the general public$$fUnrestricted
000121399 5203_ $$aDepression is strongly associated with obesity among other chronic physical diseases. The latest mega- and meta-analysis of genome-wide association studies have identified multiple risk loci robustly associated with depression. In this study, we aimed to investigate whether a genetic-risk score (GRS) combining multiple depression risk single nucleotide polymorphisms (SNPs) might have utility in the prediction of this disorder in individuals with obesity. A total of 30 depression-associated SNPs were included in a GRS to predict the risk of depression in a large case-control sample from the Spanish PredictD-CCRT study, a national multicentre, randomized controlled trial, which included 104 cases of depression and 1546 controls. An unweighted GRS was calculated as a summation of the number of risk alleles for depression and incorporated into several logistic regression models with depression status as the main outcome. Constructed models were trained and evaluated in the whole recruited sample. Non-genetic-risk factors were combined with the GRS in several ways across the five predictive models in order to improve predictive ability. An enrichment functional analysis was finally conducted with the aim of providing a general understanding of the biological pathways mapped by analyzed SNPs. We found that an unweighted GRS based on 30 risk loci was significantly associated with a higher risk of depression. Although the GRS itself explained a small amount of variance of depression, we found a significant improvement in the prediction of depression after including some non-genetic-risk factors into the models. The highest predictive ability for depression was achieved when the model included an interaction term between the GRS and the body mass index (BMI), apart from the inclusion of classical demographic information as marginal terms (AUC = 0.71, 95% CI = [0.65, 0.76]). Functional analyses on the 30 SNPs composing the GRS revealed an over-representation of the mapped genes in signaling pathways involved in processes such as extracellular remodeling, proinflammatory regulatory mechanisms, and circadian rhythm alterations. Although the GRS on its own explained a small amount of variance of depression, a significant novel feature of this study is that including non-genetic-risk factors such as BMI together with a GRS came close to the conventional threshold for clinical utility used in ROC analysis and improves the prediction of depression. In this study, the highest predictive ability was achieved by the model combining the GRS and the BMI under an interaction term. Particularly, BMI was identified as a trigger-like risk factor for depression acting in a concerted way with the GRS component. This is an interesting finding since it suggests the existence of a risk overlap between both diseases, and the need for individual depression genetics-risk evaluation in subjects with obesity. This research has therefore potential clinical implications and set the basis for future research directions in exploring the link between depression and obesity-associated disorders. While it is likely that future genome-wide studies with large samples will detect novel genetic variants associated with depression, it seems clear that a combination of genetics and non-genetic information (such is the case of obesity status and other depression comorbidities) will still be needed for the optimization prediction of depression in high-susceptibility individuals.
000121399 536__ $$9info:eu-repo/grantAgreement/ES/DGA/RD06-0018-0020-Aragon group$$9info:eu-repo/grantAgreement/ES/ISCIII-FSE/FI19-00228$$9info:eu-repo/grantAgreement/ES/ISCIII/PI12-02755$$9info:eu-repo/grantAgreement/ES/ISCIII/PI18-00238$$9info:eu-repo/grantAgreement/ES/ISCIII/PI18-00467$$9info:eu-repo/grantAgreement/ES/ISCIII/PS09-00461$$9info:eu-repo/grantAgreement/ES/ISCIII/PS09-00849$$9info:eu-repo/grantAgreement/ES/ISCIII/PS09-01095$$9info:eu-repo/grantAgreement/ES/ISCIII/PS09-02147$$9info:eu-repo/grantAgreement/ES/ISCIII/PS09-02272$$9info:eu-repo/grantAgreement/ES/ISCIII/RD06-0018$$9info:eu-repo/grantAgreement/ES/MINECO/BES-2017-082698$$9info:eu-repo/grantAgreement/ES/MINECO/IJC-2019-040080-I$$9info:eu-repo/grantAgreement/ES/MINECO-ISCIII/IFI17-00048$$9info:eu-repo/grantAgreement/ES/MINECO/RYC-2014-15774
000121399 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000121399 590__ $$a6.8$$b2022
000121399 592__ $$a2.148$$b2022
000121399 591__ $$aPSYCHIATRY$$b29 / 154 = 0.188$$c2022$$dQ1$$eT1
000121399 593__ $$aBiological Psychiatry$$c2022$$dQ1
000121399 593__ $$aPsychiatry and Mental Health$$c2022$$dQ1
000121399 593__ $$aCellular and Molecular Neuroscience$$c2022$$dQ1
000121399 594__ $$a10.2$$b2022
000121399 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000121399 700__ $$aZarza-Rebollo, Juan Antonio
000121399 700__ $$aPérez-Gutiérrez, Ana M.
000121399 700__ $$aMolina, Esther
000121399 700__ $$aGutiérrez, Blanca
000121399 700__ $$aBellón, Juan Ángel
000121399 700__ $$aMoreno-Peral, Patricia
000121399 700__ $$aConejo-Cerón, Sonia
000121399 700__ $$aAiarzagüena, Jose María
000121399 700__ $$aBallesta-Rodríguez, M. Isabel
000121399 700__ $$aFernández, Anna
000121399 700__ $$aFernández-Alonso, Carmen
000121399 700__ $$aMartín-Pérez, Carlos
000121399 700__ $$aMontón-Franco, Carmen
000121399 700__ $$aRodríguez-Bayón, Antonina
000121399 700__ $$aTorres-Martos, Álvaro
000121399 700__ $$aLópez-Isac, Elena
000121399 700__ $$aCervilla, Jorge
000121399 700__ $$aRivera, Margarita
000121399 773__ $$g12 (2022), 30 [10 pp.]$$pTransl Psychiatr$$tTranslational Psychiatry$$x2158-3188
000121399 8564_ $$s3795059$$uhttps://zaguan.unizar.es/record/121399/files/texto_completo.pdf$$yVersión publicada
000121399 8564_ $$s3032638$$uhttps://zaguan.unizar.es/record/121399/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
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000121399 951__ $$a2024-03-18-16:07:31
000121399 980__ $$aARTICLE