Complex multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidal behaviors
Daniel F Levey,
Gita A Pathak,
Frank R Wendt,
Yaira Z. Nunez,
Robert J Ursano,
Ronald C Kessler,
Henry R. Kranzler,
Murray B Stein,
Posted 18 Jan 2020
medRxiv DOI: 10.1101/2020.01.14.20017509
Posted 18 Jan 2020
Background and AimsSubstance dependence diagnoses (SDs) are important risk factors for suicidal behaviors. We investigated the associations of multiple SDs with different suicidal behaviors and tested how genetic background moderates these associations. DesignMultivariate logistic regression to investigate the associations of SDs with suicidal behaviors; structured linear mixed model to study multivariate gene- environment interactions. SettingThe Yale-Penn cohort was recruited to investigate the genetics of SDs. The Army STARRS (Study to Assess Risk and Resilience in Servicemembers) cohort was recruited to evaluate mental health risk and resilience for suicidal behaviors among Army personnel. ParticipantsYale-Penn participants (N=15,557) were assessed via the Semi-Structured Assessment for Drug Dependence and Alcoholism. Army STARRS participants (N=11,236) were evaluated using the self-administered Composite International Diagnostic Interview Screening Scales. MeasurementLifetime self-reported suicidal behaviors (ideation, SI; planning; attempt, SA); Lifetime DSM-IV diagnoses and criteria for dependence on alcohol, cannabis, cocaine (CoD), opioid (OD), and nicotine (ND) (Yale-Penn); substance use disorder (SUD) (Army STARRS). FindingsIn Yale-Penn, lifetime polysubstance dependence was strongly associated with lifetime suicidal behaviors: individuals with five SDs showed increased odds ranging from OR=6.77 (95%CI=5.74-7.99) for SI to OR=3.61 (95%CI=2.7-4.86) for SA. In Army STARRS, SUD was associated with increased odds ranging from OR=2.88 (95%CI=2.6-3.19) for SI to OR=3.92 (95%CI=3.19-4.81) for SA. In Yale-Penn, we identified multivariate gene-environment interactions (Bayes factors, BF > 0) of SI with respect to a gene cluster on chromosome 16 (LCAT, p=1.82x10-7; TSNAXIP1, p=2.13x10-7; CENPT, p=2.32x10-7; PARD6A, p=5.57x10-7) for OD (BF=12.2), CoD (BF=12.1), ND (BF=9.2), and polysubstance dependence (BF=2.1). ConclusionsComorbidity of multiple SDs is a significant suicide risk factor and heritability of suicidal behaviors is partially moderated by multivariate gene interactions.
- Downloaded 317 times
- Download rankings, all-time:
- Site-wide: 92,031
- In genetic and genomic medicine: 407
- Year to date:
- Site-wide: 75,662
- Since beginning of last month:
- Site-wide: 66,244
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!