Publication:
Body mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals.

dc.contributor.authorAnguita-Ruiz, Augusto
dc.contributor.authorZarza-Rebollo, Juan Antonio
dc.contributor.authorPerez-Gutierrez, Ana M
dc.contributor.authorMolina, Esther
dc.contributor.authorGutierrez, Blanca
dc.contributor.authorBellon, Juan Angel
dc.contributor.authorMoreno-Peral, Patricia
dc.contributor.authorConejo-Ceron, Sonia
dc.contributor.authorAiarzagüena, Jose Maria
dc.contributor.authorBallesta-Rodriguez, M Isabel
dc.contributor.authorFernandez, Anna
dc.contributor.authorFernandez-Alonso, Carmen
dc.contributor.authorMartin-Perez, Carlos
dc.contributor.authorMonton-Franco, Carmen
dc.contributor.authorRodriguez-Bayon, Antonina
dc.contributor.authorTorres-Martos, Alvaro
dc.contributor.authorLopez-Isac, Elena
dc.contributor.authorCervilla, Jorge
dc.contributor.authorRivera, Margarita
dc.contributor.funderSpanish Ministry of Health, the Institute of Health Carlos III (ISCIII), and the European Regional Development Fund
dc.contributor.funderAndalusian Council of Health
dc.contributor.funderSpanish Network of Primary Care Research, redIAPP
dc.contributor.funderMental Health, Services and Primary Care Málaga group
dc.date.accessioned2023-05-03T13:26:10Z
dc.date.available2023-05-03T13:26:10Z
dc.date.issued2022-01-04
dc.description.abstractDepression 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.
dc.description.sponsorshipThis study was funded by the Spanish Ministry of Health, the Institute of Health Carlos III (ISCIII), and the European Regional Development Fund (grants PS09/02272, PS09/02147, PS09/01095, PS09/00849, PS09/00461, and PI12-02755); the Andalusian Council of Health (grant PI-0569-2010); the Spanish Network of Primary Care Research, redIAPP (grant RD06/0018); the Aragón group (grant RD06/0018/0020); the Bizkaya group (grant RD06/0018/0018); the Castilla-León group (grant RD06/0018/0027); the Mental Health Barcelona Group (grant RD06/0018/0017); the Mental Health, Services and Primary Care Málaga group (grant RD06/0018/0039); and the projects “PI18/00238” and “PI18/00467” funded by the Institute of Health Carlos III (Co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future”). This study was performed as part of a PhD thesis conducted within the Official Doctoral Programme in Biomedicine of the University of Granada, Spain. Augusto Anguita-Ruiz was supported by a Ministry of Economy and Competitiveness and Institute of Health Carlos III fellowship (IFI17/00048). Juan Antonio Zarza-Rebollo received financial support from the Spanish Ministry of Economy and Competitiveness (BES-2017-082698). Ana M. Pérez-Gutiérrez was supported by a grant from the Ministry of Economy and Competitiveness and Institute of Health Carlos III (FI19/00228). Elena López-Isac received financial support from the Spanish Ministry of Science and Innovation Juan de la Cierva Incorporación Program (IJC2019-040080-I), and Margarita Rivera was supported by the Ministry of Economy and Competitiveness Ramón y Cajal Program (RYC-2014-15774). The authors thank the Institute of Health Carlos III (ISCIII), the European Regional Development Fund (FEDER), the Andalusian Council of Health and Andalusian Health Service (SAS), the Primary Care Prevention and Health Promotion Research Network (redIAPP), the Biomedical Research Institute of Málaga (IBIMA), and the Biomedical Research Centre (CIBM) from the University of Granada for their economic and logistic support. The authors thank all the patients and General Practitioners who participated in the trial.
dc.description.versionSi
dc.identifier.citationAnguita-Ruiz A, Zarza-Rebollo JA, Pérez-Gutiérrez AM, Molina E, Gutiérrez B, Bellón JÁ, et al. Body mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals. Transl Psychiatry. 2022 Jan 24;12(1):30.
dc.identifier.doi10.1038/s41398-022-01783-7
dc.identifier.essn2158-3188
dc.identifier.pmcPMC8786870
dc.identifier.pmid35075110
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786870/pdf
dc.identifier.unpaywallURLhttps://www.nature.com/articles/s41398-022-01783-7.pdf
dc.identifier.urihttp://hdl.handle.net/10668/19512
dc.issue.number1
dc.journal.titleTranslational psychiatry
dc.journal.titleabbreviationTransl Psychiatry
dc.language.isoen
dc.organizationÁrea de Gestión Sanitaria Nordeste de Granada
dc.organizationInstituto de Investigación Biosanitaria de Granada (ibs.GRANADA)
dc.organizationJaén
dc.organizationArea de Gestión Sanitaria Norte de Jaén
dc.organizationValle del Guadalhorce
dc.organizationInstituto de Investigación Biomédica de Málaga-IBIMA
dc.organizationAGS- Nordeste de Granada
dc.organizationAGS - Norte de Jaén
dc.page.number10
dc.provenanceRealizada la curación de contenido 29/08/2024
dc.publisherNature Publishing Group
dc.pubmedtypeJournal Article
dc.pubmedtypeMeta-Analysis
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.projectIDRD06/0018
dc.relation.projectIDPI-0569-2010
dc.relation.projectIDPI12-02755
dc.relation.projectIDPS09/02272
dc.relation.projectIDPS09/02147
dc.relation.projectIDPS09/01095
dc.relation.projectIDPS09/00849
dc.relation.projectIDS09/00461
dc.relation.projectIDPI12-02755
dc.relation.projectIDRD06/0018/0039
dc.relation.publisherversionhttps://doi.org/10.1038/s41398-022-01783-7
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectDepression
dc.subjectGenomics
dc.subject.decsDepresión
dc.subject.decsEnsayos clínicos controlados
dc.subject.decsAleatorios como asunto
dc.subject.decsEstudio de asociación del genoma complet
dc.subject.decsEstudios multicéntricos como asunto
dc.subject.decsFactores de riesgo
dc.subject.decsHumanos
dc.subject.decsPolimorfismo de nucleótido simple
dc.subject.decsPredisposición genética a la enfermedad
dc.subject.decsÍndice de Masa Corporal
dc.subject.meshBody Mass Index
dc.subject.meshDepression
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshGenome-Wide Association Study
dc.subject.meshHumans
dc.subject.meshMulticenter Studies as Topic
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshRandomized Controlled Trials as Topic
dc.subject.meshRisk Factors
dc.titleBody mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number12
dspace.entity.typePublication

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