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- Baker, J. H., et al.
(author)
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Sex differences and developmental stability in genetic and environmental influences on psychoactive substance consumption from early adolescence to young adulthood
- 2011
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In: Psychological Medicine. - New York, USA : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 41:9, s. 1907-1916
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Journal article (peer-reviewed)abstract
- Background: Genetic and environmental factors are important in the etiology of substance use. However, little is known about the stability of these factors across development. We aimed to answer three crucial questions about this etiology that have never been addressed in a single study: (1) Is there a general vulnerability to substance consumption from early adolescence to young adulthood? (2) If so, do the genetic and environmental influences on this vulnerability change across development? (3) Do these developmental processes differ in males and females?Method: Subjects included 1480 twin pairs from the Swedish Twin Study of Child and Adolescent Development who have been followed since 1994. Prospective, self-reported regular smoking, alcohol intoxication and illicit drug use were assessed at ages 13-14, 16-17 and 19-20 years. Structural modeling was performed with the program Mx.Results: An underlying common factor accounted for the association between smoking, alcohol and illicit drug consumption for the three age groups. Common genetic and shared environmental effects showed substantial continuity. In general, as participants aged, the influence of the shared environment decreased, and genetic effects became more substance specific in their effect.Conclusions: The current report answers three important questions in the etiology of substance use. The genetic and environmental risk for substance consumption is partly mediated through a common factor and is partly substance specific. Developmentally, evidence was strongest for stability of common genetic effects, with less evidence for genetic innovation. These processes seem to be the same in males and females.
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- Ji, Jianguang, et al.
(author)
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Response to Commentary by Pedersen et al.
- 2013
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In: Schizophrenia Bulletin. - : Oxford University Press (OUP). - 1745-1701 .- 0586-7614. ; 39:3, s. 506-506
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Journal article (peer-reviewed)
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- Kendler, K. S., et al.
(author)
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A latent class analysis of drug abuse in a national Swedish sample
- 2013
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In: Psychological Medicine. - 1469-8978. ; 43:10, s. 2169-2178
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Journal article (peer-reviewed)abstract
- Background. Drug abuse (DA) is a clinically heterogeneous syndrome. Using medical, legal, death and pharmacy records covering the entire population of Sweden, could we uncover meaningful subtypes of DA? Method. We performed a latent class analysis (LCA) on all individuals in Sweden born 1950-1993 who were registered with DA or its consequences (n=192 501) and then validated these classes using demographics, patterns of co-morbidity with alcohol use disorder (AUD), non-DA crime and psychiatric illness, and the pattern of aggregation and co-aggregation in sibling pairs. Results. The best-fit LCA had six classes : (1) low-frequency pure criminal, (2) high-frequency medical criminal, (3) low-frequency pure medical, (4) high-frequency medical, (5) prescription and (6) death. Each class had a distinct pattern of demographic features and co-morbidity and aggregated within sibling pairs with at least moderate specificity. For example, class 2 was characterized by early age at registration, low educational attainment, high male preponderance, high rates of AUDs, strong resemblance within sibling pairs [odds ratio (OR) 12.6] and crime and the highest risk for DA in siblings (20.0 %). By contrast, class 5 had a female preponderance, late age at registration, low rates of crime and AUDs, high rates of psychiatric illness, high familiality within sibling pairs (OR 14.7) but the lowest observed risk for DA in siblings (8.9 %). Conclusions. DA as assessed by public records is a heterogeneous syndrome. Familial factors contribute substantially to this heterogeneity. Advances in our understanding of etiological processes leading to DA will be aided by a consideration of this heterogeneity.
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| 15. |
- Kendler, K. S., et al.
(author)
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A Swedish national adoption study of criminality
- 2014
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In: Psychological Medicine. - 1469-8978. ; 44:9, s. 1913-1925
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Journal article (peer-reviewed)abstract
- Background To clarify the role of genetic and environmental factors in criminal behavior (CB), we examined all CB and violent and non-violent subtypes (VCB and NVCB, respectively) in a Swedish national sample of adoptees and their relatives. Method CB was defined by a conviction in the Swedish Crime Register with standard definitions for VCB and NVCB subtypes. We examined adoptees born 1950-1991 (n=18070) and their biological (n=79206) and adoptive (n=47311) relatives. Results The risk for all CB was significantly elevated in the adopted-away offspring of biological parents of which at least one had CB [odds ratio (OR) 1.5, 95% confidence interval (CI) 1.4-1.6] and in the biological full and half-siblings of CB adoptees (OR 1.4, 95% CI 1.2-1.6 and OR 1.3, 95% CI 1.2-1.3, respectively). A genetic risk index (including biological parental/sibling history of CB and alcohol abuse) and an environmental risk index (including adoptive parental and sibling CB and a history of adoptive parental divorce, death, and medical illness) both strongly predicted probability of CB. These genetic and environmental risk indices acted additively on adoptee risk for CB. Moderate specificity was seen in the transmission of genetic risk for VCB and NVCB between biological parents and siblings and adoptees. Conclusions CB is etiologically complex and influenced by a range of genetic risk factors including a specific liability to CB and a vulnerability to broader externalizing behaviors, and by features of the adoptive environment including parental CB, divorce and death. Genetic risk factors for VCB and NVCB may be at least partially distinct.
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| 16. |
- Kendler, K. S., et al.
(author)
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Environmental influences on familial resemblance for drug abuse in first-cousin pairs: a Swedish national study
- 2014
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In: Psychological Medicine. - 1469-8978. ; 44:2, s. 371-379
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Journal article (peer-reviewed)abstract
- Background Using three independent methods, prior studies in Swedish sibling pairs indicate that environmental factors contribute substantially to familial aggregation for drug abuse (DA). Could we replicate these results in cousin pairs? Method Using multiple Swedish public databases (1964-2011), we defined DA using medical, legal or pharmacy registry records and examined concordance in full cousin pairs as a function of age differences, younger-older relationships and geographical proximity while growing up. Results Replicating prior results in siblings, cousin pairs were significantly more similar in their history of DA if they were (i) closer versus more distant in age and (ii) grew up in high versus low geographical proximity to one another. Furthermore, controlling for background factors, having an older cousin with DA conveys a greater risk for DA than having a younger drug-abusing cousin. The greater transmission of DA from older to younger versus younger to older cousin was more prominent in pairs who grew up close to one another. In age difference and geographical proximity analyses, effects were consistently strongest in male-male cousin pairs. In analyses of older -> younger versus younger -> older transmission, effects were stronger in male-male and male-female than in female-female or female-male relative pairs. Conclusions In accord with prior results in siblings, environmental factors contribute substantially to the familial aggregation of DA in cousins and these effects are, in general, stronger in males than in females.
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| 17. |
- Kendler, K S, et al.
(author)
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Genetic and environmental risk factors in males for self-report externalizing traits in mid-adolescence and criminal behavior through young adulthood
- 2013
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In: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 43:10, s. 2161-2168
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Journal article (peer-reviewed)abstract
- BACKGROUND: Externalizing traits or behaviors are typically assessed by self-report scales or criminal records. Few genetically informative studies have used both methods to determine whether they assess the same genetic or environmental risk factors.METHOD: We examined 442 male Swedish twin pairs with self-reported externalizing behaviors at age 16–17 years [externalizing traits (EXT), self-reported delinquency (SRD), impulsivity (IMP), grandiosity (GRD) and callousness (CLS)] and criminal behavior (CB) from the National Suspect Registry from age 13 to 25 years. Multivariate structural equation modeling was conducted with Mx.RESULTS: The best-fit model contained one genetic, one shared environmental and two non-shared environmental common factors, and variable specific genetic and non-shared environmental factors. The risk for CB was influenced substantially by both genetic (a2=0.48) and familial–environmental factors (c2=0.22). About one-third of the genetic risk for CB but all of the shared environmental risk was indexed by the self-report measures. The degree to which the individual measures reflected genetic versus familial–environmental risks for CB varied widely. GRD and CLS were correlated with CB mainly through common genetic risk factors. SRD and CB covaried largely because of shared familial–environmental factors. For EXT and IMP, observed correlations with CB resulted in about equal parts from shared genetic and shared familial–environmental factors.CONCLUSIONS: In adolescence, measures of grandiose and callous temperament best tap the genetic liability to CB.Measures of antisocial behaviors better index familial–environmental risks for CB. A substantial proportion of the genetic risk to CB was not well reflected in any of the self-report measures.
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| 18. |
- Ruderfer, D M, et al.
(author)
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Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia.
- 2014
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In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 19:9, s. 1017-1024
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Journal article (peer-reviewed)abstract
- Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study (GWAS) of 19779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case-control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a novel locus near PIK3C2A. We create a polygenic risk score that is significantly different between BP and SCZ and show a significant correlation between a BP polygenic risk score and the clinical dimension of mania in SCZ patients. Our results indicate that first, combining diseases with similar genetic risk profiles improves power to detect shared risk loci and second, that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects. Identifying these loci should aid in the fundamental understanding of how these diseases differ biologically. These findings also indicate that combining clinical symptom dimensions and polygenic signatures could provide additional information that may someday be used clinically.Molecular Psychiatry advance online publication, 26 November 2013;
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| 19. |
- Smoller, JW, et al.
(author)
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Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
- 2013
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In: Lancet. - 1474-547X. ; 381:9875, s. 1371-9
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Journal article (peer-reviewed)abstract
- Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.
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| 21. |
- Wichers, M., et al.
(author)
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Genetic innovation and stability in externalizing problem behavior across development : a multi-informant twin study
- 2013
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In: Behavior Genetics. - New York, USA : Springer. - 0001-8244 .- 1573-3297. ; 43:3, s. 191-201
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Journal article (peer-reviewed)abstract
- The use of cross-informant ratings in previous longitudinal studies on externalizing behavior may have obscured the presence of continuity of genetic risk. The current study included latent factors representing the latent estimates of externalizing behavior based on both parent and self-report which eliminated rater-specific effects from these latent estimates. Symptoms of externalizing behavior of 1,480 Swedish twin pairs were obtained at ages 8-9, 13-14, 16-17 and 19-20 both by parent and self-report. Mx modeling was used to estimate additive genetic, shared and specific environmental influences. Genetic continuity was found over the entire developmental period as well as additional sources of genetic influence emerging around early and late adolescence. New unique environmental effects (E) on externalizing behavior arose early in adolescence. The results support both the presence of genetic continuity and change in externalizing behavior during adolescence due to newly emerging genetic and environmental risk factors.
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