e97cbafec91667ee57daf5286df26540 pmc_9864492.pdf ebfb869512dc8d0371ba6ada3526e78083e192a0 pmc_9864492.pdf 8e4daed483e7672b2de753cd5d0dfef73494af1933ac0e7596d1e168ae923174 pmc_9864492.pdf Title: Underlying Mechanisms Involved in Gambling Disorder Severity: A Pathway Analysis Considering Genetic, Psychosocial, and Clinical Variables Subject: Gambling Disorder (GD) has a complex etiology that involves biological and environmental aspects. From a genetic perspective, neurotrophic factors (NTFs) polymorphisms have been associated with the risk of developing GD. The aim of this study was to assess the underlying mechanisms implicated in GD severity by considering the direct and mediational relationship between different variables including genetic, psychological, socio-demographic, and clinical factors. To do so, we used genetic variants that were significantly associated with an increased risk for GD and evaluated its relationship with GD severity through pathway analysis. We found that the interaction between these genetic variants and other different biopsychological features predicted a higher severity of GD. On the one hand, the presence of haplotype block 2, interrelated with haplotype block 3, was linked to a more dysfunctional personality profile and a worse psychopathological state, which, in turn, had a direct link with GD severity. On the other hand, having rs3763614 predicted higher general psychopathology and therefore, higher GD severity. The current study described the presence of complex interactions between biopsychosocial variables previously associated with the etiopathogenesis and severity of GD, while also supporting the involvement of genetic variants from the NTF family. Keywords: gambling disorder; severity; neurotrophic genes; socio-demographics; personality traits; psychopathology Author: Neus Solé-Morata, Isabel Baenas, Mikel Etxandi, Roser Granero, Manel Gené, Carme Barrot, Mónica Gómez-Peña, Laura Moragas, Nicolas Ramoz, Philip Gorwood, Fernando Fernández-Aranda and Susana Jiménez-Murcia Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Jan 13 10:05:22 2023 CET ModDate: Fri Jan 13 10:21:09 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1011239 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CFDLTT+URWPalladioL-Bold Type 1 Custom yes yes no 10 0 QRPVZK+URWPalladioL-Roma Type 1 Custom yes yes no 15 0 ZDDHVA+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 EWZHMZ+VnURWPalladioL Type 1 Custom yes yes no 23 0 ZZTQUO+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 HGMNRX+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 ZIPEAN+EURM10 Type 1 Builtin yes yes no 74 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes no 84 0 FXXUVH+CMSY10 Type 1 Builtin yes yes no 92 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 100 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 104 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 108 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 112 0 SymbolMT CID TrueType Identity-H yes no yes 119 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 136 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 140 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 144 0 SLGZGC+VnURWPalladioL-Italic Type 1 Custom yes yes no 165 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-22 02:31:41 CEST RepresentationInformation: pmc_9864492.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-01-26 02:11:47 CET Size: 1011239 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 447 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Participants and Procedure Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Clinical Measurements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Other Variables Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Genetic Information Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Description of the Participants and Distribution of the Genetic Measures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Path Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Info: Title: Underlying Mechanisms Involved in Gambling Disorder Severity: A Pathway Analysis Considering Genetic, Psychosocial, and Clinical Variables Author: Neus Solé-Morata, Isabel Baenas, Mikel Etxandi, Roser Granero, Manel Gené, Carme Barrot, Mónica Gómez-Peña, Laura Moragas, Nicolas Ramoz, Philip Gorwood, Fernando Fernández-Aranda and Susana Jiménez-Murcia Subject: Gambling Disorder (GD) has a complex etiology that involves biological and environmental aspects. From a genetic perspective, neurotrophic factors (NTFs) polymorphisms have been associated with the risk of developing GD. The aim of this study was to assess the underlying mechanisms implicated in GD severity by considering the direct and mediational relationship between different variables including genetic, psychological, socio-demographic, and clinical factors. To do so, we used genetic variants that were significantly associated with an increased risk for GD and evaluated its relationship with GD severity through pathway analysis. We found that the interaction between these genetic variants and other different biopsychological features predicted a higher severity of GD. On the one hand, the presence of haplotype block 2, interrelated with haplotype block 3, was linked to a more dysfunctional personality profile and a worse psychopathological state, which, in turn, had a direct link with GD severity. On the other hand, having rs3763614 predicted higher general psychopathology and therefore, higher GD severity. The current study described the presence of complex interactions between biopsychosocial variables previously associated with the etiopathogenesis and severity of GD, while also supporting the involvement of genetic variants from the NTF family. 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