| 1. |
- Forstner, A. J., et al.
(författare)
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Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 4179-4190
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Tidskriftsartikel (refereegranskat)abstract
- Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10−4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
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| 2. |
- Carmona-Gutierrez, D., et al.
(författare)
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Guidelines and recommendations on yeast cell death nomenclature
- 2018
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Ingår i: Microbial Cell. - : Shared Science Publishers OG. - 2311-2638. ; 5:1, s. 4-31
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Forskningsöversikt (refereegranskat)abstract
- Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.
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| 5. |
- Rayner, C, et al.
(författare)
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A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 150-
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
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| 12. |
- Noh, Hyun Ji, et al.
(författare)
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Integrating evolutionary and regulatory information with multispecies approach implicates genes and pathways in obsessive-compulsive disorder
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants, of which at least six (35%) alter transcription factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide significance (p = 6.37 x 10(-11)) when we include 33,370 population-matched controls. Our findings suggest synaptic adhesion as a key component in compulsive behaviors, and show that targeted sequencing plus functional annotation can identify potentially causative variants, even when genomic data are limited.
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| 16. |
- Granville, S, et al.
(författare)
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Optical conductivity and x-ray absorption and emission study of the band structure of MnN films
- 2005
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 72:20, s. 205127-
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Tidskriftsartikel (refereegranskat)abstract
- The band structure of MnN films prepared by ion assisted deposition has been investigated by optical conductivity and x-ray absorption and emission spectroscopies. X-ray diffraction and extended x-ray absorption fine structure show the films to be nanocrystalline but phase pure and exhibiting the known antiferromagnetic distorted rocksalt phase. X-ray emission spectroscopy of the N K-edge and x-ray absorption near edge spectroscopy of both the N K- and Mn L-edges are used to probe the occupied and empty densities of states, which compare well with the N(2p) and Mn(3d) partial densities of states calculated using the linearized muffin-tin orbital band structure method. A similar comparison is made between the measured optical conductivity and the calculated contribution from interband transitions. It is possible to associate the main features in the measured spectrum with corresponding ones in the calculated optical function. The major differences between calculated and measured spectra can be understood on the basis of a limited electron mean-free-path in these nanocrystalline films, which broadens the features in the joint density of states and relaxes the momentum conservation requirement. The calculated optical functions are analyzed in detail in terms of their dominant band-to-band contributions and in addition the polarization dependence is predicted. Temperature dependent conductivity measurements are also reported and show a clear metallic behavior and a weak Kondo-like low temperature anomaly.
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| 17. |
- Isaeva, Anna A., et al.
(författare)
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New metal-rich mixed chalcogenides with intergrowth structures : Ni8.21Ge2S2 and Ni8.45Ge2Se2
- 2009
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Ingår i: Solid State Sciences. - : Elsevier BV. - 1293-2558 .- 1873-3085. ; 11:6, s. 1071-1076
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Tidskriftsartikel (refereegranskat)abstract
- New metal-rich mixed nickel germanium chalcogenides, Ni8.21(1)Ge2S2 and Ni8.45(1)Ge2Se2, were synthesized by a high-temperature ceramic technique. Ni8.21Ge2S2 decomposes incongruently at 798(5) degrees C, while Ni8.45Ge2Se2 is stable only between approximately 600(5) degrees C and 813(5) degrees C. Single crystals were grown from a molten flux and by a recrystallization of presynthesized charge. The X-ray diffraction study revealed that Ni8.21Ge2S2 and Ni8.45Ge2S2 are isostructural and crystallize in the tetragonal system (space group 14/mmm, Z = 2) with a = 3.578(1) angstrom, c = 24.687(5) angstrom, and a = 3.601 (1) angstrom, c = 25.427(6) angstrom, respectively. Their crystal structures comprise heterometallic (2)(infinity) [Ni6Ge2] slabs and are closely related to the Ni8.54Ga2Se2 and Ni8.93Sn2S2 structure types. The geometrical changes of structural units upon p-element substitution in all known Ni(10-delta)E(2)Q(2) (E = element of group 13 or 14; Q = chalcogen) compounds are discussed. The relation to the intergrowth structure of Ni5.46GeSe2 is analyzed.
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| 29. |
- Isomura, Kayoko, et al.
(författare)
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Risk of specific cardiovascular diseases in obsessive-compulsive disorder
- 2020
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Ingår i: Journal of Psychiatric Research. - : Elsevier. - 0022-3956 .- 1879-1379. ; 135, s. 189-196
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with obsessive-compulsive disorder (OCD) may have an increased risk of cardiovascular disease (CVD), but evidence for specific types of CVD is limited. This population-based, sibling-controlled cohort study investigated the risk of specific CVD in individuals with OCD. Linking data from various Swedish population-based registers, we explored the risk of a range of CVD in a cohort of individuals diagnosed with OCD between 1973 and 2013 (n = 33,561), compared to matched (1:10) unaffected individuals (n = 335,610). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using conditional Cox proportional hazards regression models, adjusting for history of somatic diseases. To control for familial confounders, we analyzed 23,263 clusters of full siblings discordant for OCD. Individuals with psychiatric comorbidities were systematically excluded to assess the impact of these comorbidities. Over an average follow-up time of 27 years, OCD was associated with an increased risk of a broad range of CVD (adjusted HR [aHR] for any CVD = 1.25 [95% confidence interval [CI], 1.22-1.29]). These associations were strongest for the subtypes venous thrombo-embolism (aHR = 1.48 [95% CI, 1.38-1.58]) and heart failure (aHR = 1.37 [95% CI, 1.28-1.46]). When comparing OCD-exposed individuals with their non-exposed full siblings, results were largely similar. Exclusion of several groups of psychiatric comorbidities resulted in comparable results, albeit attenuated. Individuals with OCD have a moderately increased risk of CVD-related morbidity, independent from history of somatic diseases, familial confounders, and psychiatric comorbidities. The time may be ripe for the development and evaluation of lifestyle interventions to help reduce the risk of cardiovascular morbidity in OCD.
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| 34. |
- Pinseel, E., et al.
(författare)
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Strain-specific transcriptional responses overshadow salinity effects in a marine diatom sampled along the Baltic Sea salinity cline
- 2022
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Ingår i: Isme Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370.
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Tidskriftsartikel (refereegranskat)abstract
- The salinity gradient separating marine and freshwater environments represents a major ecological divide for microbiota, yet the mechanisms by which marine microbes have adapted to and ultimately diversified in freshwater environments are poorly understood. Here, we take advantage of a natural evolutionary experiment: the colonization of the brackish Baltic Sea by the ancestrally marine diatom Skeletonema marinoi. To understand how diatoms respond to low salinity, we characterized transcriptomic responses of acclimated S. marinoi grown in a common garden. Our experiment included eight strains from source populations spanning the Baltic Sea salinity cline. Gene expression analysis revealed that low salinities induced changes in the cellular metabolism of S. marinoi, including upregulation of photosynthesis and storage compound biosynthesis, increased nutrient demand, and a complex response to oxidative stress. However, the strain effect overshadowed the salinity effect, as strains differed significantly in their response, both regarding the strength and the strategy (direction of gene expression) of their response. The high degree of intraspecific variation in gene expression observed here highlights an important but often overlooked source of biological variation associated with how diatoms respond to environmental change.
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| 35. |
- Ripsweden, J, et al.
(författare)
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Is training essential for interpreting cardiac computed tomography?
- 2009
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 50:2, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiac computed tomography (CT) has gained increasing acceptance for diagnosing obstructive coronary artery disease (CAD). Several guidelines have been published on required education for proficiency in the interpretation of these examinations. Purpose: To describe the learning-curve effect of the interpretation of 100 consecutive cardiac CT examinations aimed at diagnosing CAD. The diagnostic accuracy of radiologists and radiographers was also compared. Material and Methods: Two radiologists and two radiographers, all with no prior experience in evaluation of cardiac CT, independently underwent a dedicated training program of 100 examinations randomized into 10 blocks (sessions), with 10 cases in each. They independently evaluated the coronary arteries regarding significant obstructive CAD. After every session, individual feedback on diagnostic accuracy and comparison with the corresponding invasive coronary angiography (currently regarded as the gold standard to detect coronary lesions) was given. The time required for interpretation was recorded. Results: The mean review time decreased ( P<0.0001) successively during the 10 sessions for all the observers together. The first session had a mean review time of 32 min, and the last session 16 min. No significant improvement in sensitivity, specificity, or negative predictive value (NPV) was observed. For positive predictive value (PPV), there was an improvement for the radiologists ( P<0.05), but not for the radiographers. The radiographers had a higher total specificity compared to the radiologists ( P<0.01). Conclusion: The review time for novices in cardiac CT was approximately halved during the first 100 cases, with maintained accuracy. There was a learning-curve effect in PPV for the radiologists. The diagnostic accuracy of dedicated radiographers indicates that they might be considered to be included as part of the evaluation team.
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| 36. |
- Ruck, A, et al.
(författare)
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Paravalvular Aortic Regurgitation Severity Assessed by Quantitative Aortography: ACURATE neo2 versus ACURATE neo Transcatheter Aortic Valve Implantation
- 2021
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 10:20
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Tidskriftsartikel (refereegranskat)abstract
- The new-generation ACURATE neo2 system was commercially released in September 2020. In this study, we sought to compare the aortic regurgitation (AR) severity of the ACURATE neo2 versus the ACURATE neo transcatheter heart valve, using quantitative videodensitometric angiography (qAR). This is a retrospective, Corelab analysis of final post-transcatheter aortic valve implantation (TAVI) aortograms of patients treated with the ACURATE neo2 and ACURATE neo systems. The ACURATE neo2 cohort comprised consecutive patients treated between September 2020 and January 2021 at two centers. The ACURATE neo cohort included consecutive patients treated before September 2020. Our primary objective was to compare AR severity on qAR following TAVI with ACURATE neo2 and ACURATE neo. Out of 401 aortograms, 228 (56.9%) were analyzable, with 120 in the ACURATE neo2 cohort, and 108 in the ACURATE neo cohort. The mean AR fraction was 4.4 ± 4.8% in the neo2 cohort, and 9.9 ± 8.2% in the neo cohort (p < 0.001). Furthermore, moderate or severe AR (qAR > 17%) was detected in 2 aortograms (1.7%) in the neo2 cohort and 15 aortograms (13.9%) in the neo cohort (p < 0.001). Quantitative aortography shows a lower rate of moderate or severe paravalvular AR in what is the first European experience of the new-generation, self-expanding ACURATE neo2 when compared to the first-generation ACURATE neo. Moreover, aortographic data need to be correlated and compared to Core Laboratory-adjudicated 30-day echocardiographic data.
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| 40. |
- Sarkar, N., et al.
(författare)
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Effects of intramyocardial injection of phVEGF-A(165) as sole therapy in patients with refractory coronary artery disease - 12-month follow-up : Angiogenic gene therapy
- 2001
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 250:5, s. 373-381
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To test the safety and bioactivity of phVEGF-A(165) after intramyocardial injection during 12-month follow-up. Design. Open-labelled study. Subjects. Inclusion criteria were angina pectoris, Canadian Cardiovascular Society (CCS) class III-IV, unamenable to further revascularization, ejection fraction (EF) >30%, perfusion defects extending over >10% of the anterolateral left ventricle wall detectable with adenosine single photon emission computerized tomography (SPECT) and at least one patent vessel visible by coronary angiography. Seven of 39 patients referred for gene therapy were included. Intervention. Via a mini-thoracotomy under general anaesthesia, phVEGF-A(165) was injected directly into the myocardium at four sites in the anterolateral region of the left ventricle. Results. Operative procedures were uneventful. Perioperative release of myocardial markers and electrocardiogram (ECG) changes were detected in two patients. There were no perioperative deaths but one patient died 7 months postoperatively because of myocardial infarction. Plasma vascular endothelial growth factor (VEGF)-A levels increased two to threefold peaking 6 days postoperatively (P<0.004) and returning to baseline by day 30. A significant reduction in angina pectoris was reported. The CCS class improved from 3.30.2 to 1.9 +/-0.3 (P<0.01) and nitroglycerine intake decreased from 3915 to 12 +/-5 tablets week(-1) (P<0.001) 2 months after gene transfer. Improvements remained after 12 months when nitroglycerine consumption approached zero. Improved myocardial function in the phVEGF-A(165) injection region was documented in all patients (P<0.016) by tissue velocity imaging (TVI). Reduced reversible ischaemia was detected by adenosine SPECT in four patients. Improved collateralization was detected in four patients with coronary angiography. Conclusion. Intramyocardial injection of phVEGF-A(165) is safe and may lead to improved myocardial perfusion and function with longstanding symptomatic relief in end-stage angina pectoris. Based on these results this therapeutic potential is being tested in a double-blind placebo controlled multicentre trial, EUROINJECT ONE.
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| 41. |
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| 42. |
- Svensson, A, et al.
(författare)
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Heart rate variability and heat sensation during CT coronary angiography: Low-osmolar versus iso-osmolar contrast media
- 2010
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 51:7, s. 722-726
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Tidskriftsartikel (refereegranskat)abstract
- Background: During computed tomography coronary angiography (CTCA) unexpected changes in heart rate while scanning may affect image quality. Purpose: To evaluate whether an iso-osmolar contrast medium (IOCM, iodixanol) and a low-osmolar contrast medium (LOCM, iomeprol) affect heart rate and experienced heat sensation differently. Material and Methods: One hundred patients scheduled for CTCA were randomized to receive either iodixanol 320 mgI/ml or iomeprol 400 mgI/ml. Depending on their heart rate, the patients were assigned to one of five scanning protocols, each optimized for different heart rate ranges. During scanning the time between each heart beat (hb) was recorded, and the corresponding heart rate was calculated. For each contrast medium (CM) the average heart rate, the variation in heart rate from individual mean heart rate, and the mean deviation from the predefined scanning protocol were calculated. Experience of heat was obtained immediately after scanning by using a visual analog scale (VAS). Examination quality was rated by two radiologists on a three-point scale. Results: The mean variation in heart rate after IOCM was 1.4 hb/min and after LOCM it was 4.4 hb/min (NS). The mean deviations in heart rate from that in the predefined scanning protocol were 2.0 hb/min and 4.7 hb/min, respectively (NS). A greater number of arrhythmic hb were observed after LOCM compared with IOCM ( P<0.001). There was no statistically significant difference in image quality. The LOCM group reported a stronger heat sensation after CM injection than the IOCM group (VAS =36 mm and 18 mm, P<0.05). Conclusion: At clinically used concentrations the IOCM, iodixanol 320 mgI/ml, does not increase the heart rate during CTCA and causes less heart arrhythmia and less heat sensation than the LOCM, iomeprol 400 mgI/ml.
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| 43. |
- Sylven, C., et al.
(författare)
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Myocardial Doppler tissue velocity improves following myocardial gene therapy with VEGF-A(165) plasmid in patients with inoperable angina pectoris
- 2001
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Ingår i: Coronary Artery Disease. - : Ovid Technologies (Wolters Kluwer Health). - 0954-6928 .- 1473-5830. ; 12:3, s. 239-243
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Tidskriftsartikel (refereegranskat)abstract
- Background Myocardial tissue velocity and perfusion were studied in patients with severe angina pectoris following gene therapy by intramyocardial injection of phVEGF-A(165) via thoracotomy. Plasma concentrations of VEGF-A increased postoperatively. Two months after treatment anginal status and myocardial tissue velocity improved and perfusion showed a tendency to improve. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy. Objective To study effects on myocardial tissue velocity and perfusion in patients with angina pectoris following intramyocardial injection of phVEGF-A(165) via thoracotomy. Design Open label, phase I/II. Methods Six patients with Canadian Cardiovascular Society (CCS) angina pectoris functional Glass III - IV and with major defects at adenosine stress single-photon emission computerized tomography (SPECT) were studied. In addition to SPECT, coronary angiography and dobutamine stress echocardiography with tissue Doppler velocity imaging were performed before and two months after gene transfer. Results Plasma concentrations of VEGF-A increased 2 to 3 times (P < 0.04) over baseline from 2 to 14 days after injection with normalization after 4 weeks. The CCS class improved about 40%, from 3.3 +/- 0.2 to 2.0 +/- 0.3 (P < 0.02) and nitroglycerine consumption decreased 30 - 40%, from 44 +/- 17 to 15 +/- 5 tablets per week (P < 0.05). The maximal systolic myocardial tissue velocity increased in all patients about 25% (P < 0.02) but did not reach the reference range. Myocardial perfusion at SPECT improved in four of the six patients. Conclusions Anginal status, myocardial tissue velocity and perfusion can be improved by phVEGF-A(165) intramyocardial injection. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy. Coron Artery Dis 12:239-243
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| 48. |
- Virtanen, S., et al.
(författare)
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Association of Obsessive-Compulsive Disorder and Obsessive-Compulsive Symptoms With Substance Misuse in 2 Longitudinal Cohorts in Sweden
- 2022
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Neurobiological models have postulated shared neural mechanisms between obsessive-compulsive disorder (OCD) and substance use disorders, but results from clinical and epidemiological studies are conflicting or even suggest that OCD may be protective against substance misuse. OBJECTIVE To investigate whether OCD and obsessive-compulsive symptoms are associated with substance misuse and the extent to which shared genetic and/or environmental factors account for this association. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, individuals in the general population of Sweden born between January 1, 1932, and December 31, 1997 (population cohort), were followed up through Swedish nationwide registers from January 1,1997. to December 31. 2013. The second cohort included twin participants in the Child and Adolescent Twin Study in Sweden (CATSS) followed up from ages 18 to 24 years. Data were analyzed from March 1, 2021, to March 31, 2022. EXPOSURES Lifetime International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of OCD in the National Patient Register (population cohort 1), and self-reported obsessive-compulsive symptoms at 18 years of age (CATSS cohort). MAIN OUTCOMES AND MEASURES Substance misuse was defined as registered substance use-related disorder, criminal conviction, or death (population cohort), and self-reported alcohol and drug dependence symptoms at 18 and 24 years of age (CATSS cohort). RESULTS The general population cohort included 6 304188 individuals (48.9% women and 51.1% men; median baseline age, 30.5 [IQR, 15.0-46.4] years), of whom 27 342 had an OCD diagnosis. Obsessive-compulsive disorder was associated with an elevated risk of substance misuse (hazard ratio, 3.68 [95% CI, 3.52-3.85]). In the 9230 individuals in the CATSS cohort (5551 women [60.1%] and 3679 men [39.9%]), obsessive-compulsive symptoms at 18 years of age were associated with increased symptoms of alcohol dependence (concurrent [n = 9219], beta = 0.18 [95% CI, 0.16-0.20]; longitudinal [n = 3381], beta = 0.10 [95% CI, 0.06-0.14]) and drug dependence (concurrent [n = 749], beta = 0.19 [95% CI, 0.11-0.27]; longitudinal [n = 452]. beta = 0.15 [95% CI, 0.04-0.25]). Comorbid anxiety and depression did not entirely explain the associations in either cohort. Using data from full siblings and maternal half-siblings (population cohort) and monozygotic and dizygotic twins (CATSS cohort) provided estimates of the relative contribution of genetic and environmental influences to the covariance between OCD and obsessive-compulsive symptoms and substance misuse or dependence. The associations were explained by genetic (56%-68%) and nonshared environmental (32%-44%) factors. CONCLUSIONS AND RELEVANCE The findings of this Swedish population-based cohort study challenge the notion that OCD is protective against developing substance misuse. The association of OCD and obsessive-compulsive symptoms with substance misuse was largely explained by shared genetics but was also compatible with partial environmental mediation.
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