| 1. |
- Luningham, J. M., et al.
(författare)
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Data Integration Methods for Phenotype Harmonization in Multi-Cohort Genome-Wide Association Studies With Behavioral Outcomes
- 2019
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Parallel meta-analysis is a popular approach for increasing the power to detect genetic effects in genome-wide association studies across multiple cohorts. Consortia studying the genetics of behavioral phenotypes are oftentimes faced with systematic differences in phenotype measurement across cohorts, introducing heterogeneity into the meta-analysis and reducing statistical power. This study investigated integrative data analysis (IDA) as an approach for jointly modeling the phenotype across multiple datasets. We put forth a bi-factor integration model (BFIM) that provides a single common phenotype score and accounts for sources of study-specific variability in the phenotype. In order to capitalize on this modeling strategy, a phenotype reference panel was utilized as a supplemental sample with complete data on all behavioral measures. A simulation study showed that a mega-analysis of genetic variant effects in a BFIM were more powerful than meta-analysis of genetic effects on a cohort-specific sum score of items. Saving the factor scores from the BFIM and using those as the outcome in meta-analysis was also more powerful than the sum score in most simulation conditions, but a small degree of bias was introduced by this approach. The reference panel was necessary to realize these power gains. An empirical demonstration used the BFIM to harmonize aggression scores in 9-year old children across the Netherlands Twin Register and the Child and Adolescent Twin Study in Sweden, providing a template for application of the BFIM to a range of different phenotypes. A supplemental data collection in the Netherlands Twin Register served as a reference panel for phenotype modeling across both cohorts. Our results indicate that model-based harmonization for the study of complex traits is a useful step within genetic consortia.
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| 2. |
- Andersson, Anneli, 1992-, et al.
(författare)
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Genetic overlap between ADHD and externalizing, internalizing and neurodevelopmental disorder symptoms : a systematic review and meta-analysis
- 2018
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Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 48:6, s. 455-456
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder (Wilens, Biederman & Spencer 2002) and affects approximately 5% of children (Polanczyk, de Lima, Horta, Biederman & Rohde 2007). About half of those diagnosed in childhood continue to have the diagnosis and symptoms in adulthood (Kessler et al. 2006). The co-occurrence of ADHD with other psychiatric disorder symptoms (Burt et al. 2001; Cole et al. 2009; Polderman et al. 2014) has been suggested to be partly explained by a shared genetic vulnerability (Polderman et al. 2014). However, the strength of the genetic overlap is currently unclear. Also, no study has examined whether the genetic correlations differs between age groups (childhood versus adulthood), by rater (self-report, other informant, combined (parent-teacher, parent-twin, teacher-twin)), or by type of psychiatric disorder symptoms (externalizing, internalizing, neu-rodevelopmental). To address this gap, we conducted a systematic literature search to identify relevant twin studies, in PubMed, PsycINFO, and EMBASE. A total of 31 articles were identified and included in the present study. The pooled estimates showed that the comorbidity between ADHD and diverse psychiatric disorder symptoms were explained by shared genetic effectsrg= 0.50 (0.43–0.56). A similar shared genetic overlap between ADHD and psychiatric disorder symptoms was observed in both childhood rg= 0.51(0.42–0.61) and adulthood rg= 0.47 (0.40–0.53). Similar results werealso found for self-reports rg= 0.49 (0.42–0.55), other informants rg= 0.50 (0.40–0.60), and combined raters rg= 0.51 (0.30–0.69). Further, the strength of the genetic correlations of ADHD with the externalizing rg= 0.49 (0.39–0.59), internalizing rg= 0.55 (0.40–0.68) and neurodevelopmental rg= 0.47 (0.40–0.53) spectrums were similar in magnitude. These findings emphasize the presence of a shared genetic liability between ADHD and externalizing, internalizing and neurodevelopmental disorder symptoms, independent of age and rater.ReferencesBurt, S. A., Krueger, R. F., McGue, M., Iacono, W. G. (2001).Sources of covariation among attention-deficit/hyperactivity disorder,oppositional defiant disorder, and conduct disorder: the importance ofshared environment.Journal of Abnormal Psychology, 4, 516–525.Cole, J., Ball, H. A., Martin, N. C., Scourfield, J., McGuffin, P.(2009). Genetic overlap between measures of hyperactivity/inatten-tion and mood in children and adolescents.J Am Acad Child AdolescPsychiatry48, 1094–1101.Kessler, R. C., Adler, L., Barkley, R., Biederman, J., Conners, C.K., Demler, O., Faraone, S. V., Greenhill, L. L., Howes, M. J., Secnik,K., Spencer, T., Ustun, T. B., Walters, E. E., Zaslavsky, A. M. (2006).The prevalence and correlates of adult ADHD in the United States:results from the National Comorbidity Survey Replication.Am JPsychiatry, 163, 716–723.Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., Rohde,L. A. (2007). The worldwide prevalence of ADHD: a systematicreview and metaregression analysis.Am J Psychiatry, 164, 942-8.Polderman, T. J., Hoekstra, R. A., Posthuma, D., Larsson, H.(2014). The co-occurrence of autistic and ADHD dimensions inadults: an etiological study in 17,770 twins.Transl Psychiatry2014;4: e435.Wilens, T. E., Biederman, J., Spencer, T. J. (2002). Attentiondeficit/hyperactivity disorder across the lifespan.Annual Review Med53:113–131.
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| 3. |
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| 4. |
- Brikell, Isabell, et al.
(författare)
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Heritability of attention-deficit hyperactivity disorder in adults
- 2015
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Ingår i: American Journal of Medical Genetics Part B. - Hoboken, USA : Wiley-Blackwell. - 1552-4841 .- 1552-485X. ; 168:6, s. 406-413
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Forskningsöversikt (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Symptoms often persist into adulthood, with a prevalence of 2.5-5% in adult populations. Twin studies in childhood consistently report high heritabilities of 70-80%, while studies in adult samples show only moderate heritability of 30-40% when estimated from self-ratings. This review summarizes the available research on the heritability of ADHD in adults. Three key findings are outlined: (i) self-ratings lead to relatively low heritability estimates of ADHD, independent of age and whether ratings refer to current or retrospective symptoms; (ii) studies relying on different informants to rate each twin within a pair (i.e., self-ratings and different parents/teachers rating each twin in a pair) consistently yield lower heritability estimates than studies relying on ratings from a single informant; (iii) studies using cross-informant data via either combined parent and self-ratings or clinical diagnoses information suggest that the heritability of ADHD in adults could be as high as 70-80%. Together, the reviewed studies suggest that the previously reported low heritability of ADHD in adults is unlikely to reflect a true developmental change. Instead, the drop in heritability is better explained by rater effects related to a switch from using one rater for both twins in a pair (parent/teacher) in childhood, to relying on self-ratings (where each twin rates themselves) of ADHD symptoms in adulthood. When rater effects are addressed using cross-informant approaches, the heritability of ADHD in adults appears to be comparable to the heritability of ADHD in childhood.
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| 5. |
- Burt, S. Alexandra, et al.
(författare)
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Additional evidence against shared environmental contributions to attention-deficit/hyperactivity problems
- 2012
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Ingår i: Behavior Genetics. - New York, USA : Springer. - 0001-8244 .- 1573-3297. ; 42:5, s. 711-721
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Tidskriftsartikel (refereegranskat)abstract
- A recent meta-analysis "Burt (Psychol Bull 135:608-637, 2009)" indicated that shared environmental influences (C) do not contribute to Attention-Deficit/Hyperactivity Disorder (ADHD). Unfortunately, the meta-analysis relied almost exclusively on classical twin studies. Although useful in many ways, some of the assumptions of the classical twin model (e.g., dominant genetic and shared environmental influences do not simultaneously influence the phenotype) can artifactually decrease estimates of C. There is thus a need to confirm that dominant genetic influences are not suppressing estimates of C on ADHD. The current study sought to do just this via the use of a nuclear twin family model, which allows researchers to simultaneously model and estimate dominant genetic and shared environmental influences. We examined two independent samples of child twins: 312 pairs from the Michigan State University Twin Registry and 854 pairs from the PrE School Twin Study in Sweden. Shared environmental influences were found to be statistically indistinguishable from zero and to account for less than 5 % of the variance. We conclude that the presence of dominant genetic influences does not account for the absence of C on ADHD.
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| 6. |
- Chen, Tian-Jiao, et al.
(författare)
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Genetic and environmental influences on the relationship between ADHD symptoms and internalizing problems : A Chinese twin study
- 2016
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Ingår i: American Journal of Medical Genetics Part B. - Hoboken, USA : John Wiley & Sons. - 1552-4841 .- 1552-485X. ; 171:7, s. 931-937
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Tidskriftsartikel (refereegranskat)abstract
- Several twin studies have investigated the overlap between attention deficit hyperactivity disorder (ADHD) and externalizing problems; however, limited information is known regarding the genetic and environmental contribution to the overlap between ADHD and internalizing problems. This study examined the genetic and environmental influences on the variation in and covariation between ADHD symptoms and internalizing problems by using the Child Behavior Checklist (CBCL). We investigated 1,316 child and adolescent twins, including 780 monozygotic twins and 536 dizygotic twins, aged 6 years to 18 years from the Chinese Child and Adolescent Twin Registry. ADHD symptoms and internalizing problems were quantified through parent rating by using the Attention Problems Scale and other three scales, which include Anxious/Depressed, Withdrawn, and Somatic Complaints of CBCL. Genetic and environmental susceptibilities common to ADHD symptoms and internalizing problems were examined through bivariate twin modeling. Results showed that genetic factors substantially influenced the ADHD symptoms with a heritability of 72%. Modest genetic influences and substantial shared environmental influences (20-77%) were observed in the three internalizing problem scales. Common genetic and shared environmental influences were essential for the overlap between ADHD and the three internalizing problems respectively. Approximately one-fifth of the genetic variance of ADHD symptoms was shared with anxiety/depression. In conclusion, substantial genetic and shared environmental influences on ADHD symptoms and internalizing problems were observed in Chinese children and adolescents. Our finding supports a common etiology between ADHD and internalizing problems. This finding can also help explain the co-existence of these behavior problems. © 2015 Wiley Periodicals, Inc.
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| 7. |
- D'Onofrio, Brian M., et al.
(författare)
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Translational Epidemiologic Approaches to Understanding the Consequences of Early-Life Exposures
- 2016
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Ingår i: Behavior Genetics. - New York, USA : Springer. - 0001-8244 .- 1573-3297. ; 46:3, s. 315-328
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Forskningsöversikt (refereegranskat)abstract
- Prominent developmental theories posit a causal link between early-life exposures and later functioning. Yet, observed associations with early exposures may not reflect causal effects because of genetic and environmental confounding. The current manuscript describes how a systematic series of epidemiologic analyses that combine several genetically-informative designs and statistical approaches can help distinguish between competing theories. In particular, the manuscript details how combining the use of measured covariates with sibling-comparisons, cousin-comparisons, and additional designs can help elucidate the sources of covariation between early-life exposures and later outcomes, including the roles of (a) factors that are not shared in families, including a potential causal effect of the exposure; (b) carryover effects from the exposure of one child to the next; and (c) familial confounding. We also describe key assumptions and how they can be critically evaluated. Furthermore, we outline how subsequent analyses, including effect decomposition with respect to measured, plausible mediators, and quantitative genetic models can help further specify the underlying processes that account for the associations between early-life exposures and offspring outcomes.
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| 8. |
- Gustafsson, Per, et al.
(författare)
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Heritability of cortisol regulation in children.
- 2011
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Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Australian Academic Press. - 1832-4274 .- 1839-2628. ; 14:6, s. 553-61
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Tidskriftsartikel (refereegranskat)abstract
- The normal development of cortisol regulation during childhood is thought to be influenced by a complex interplay between environmental and genetic factors.
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| 9. |
- Magnusson, Patrik K. E., et al.
(författare)
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The Swedish Twin Registry : establishment of a biobank and other recent developments
- 2013
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Ingår i: Twin Research and Human Genetics. - Cambridge, United Kingdom : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 16:1, s. 317-329
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Twin Registry (STR) today contains more than 194,000 twins and more than 75,000 pairs have zygosity determined by an intra-pair similarity algorithm, DNA, or by being of opposite sex. Of these, approximately 20,000, 25,000, and 30,000 pairs are monozygotic, same-sex dizygotic, and opposite-sex dizygotic pairs, respectively. Since its establishment in the late 1950s, the STR has been an important epidemiological resource for the study of genetic and environmental influences on a multitude of traits, behaviors, and diseases. Following large investments in the collection of biological specimens in the past 10 years we have now established a Swedish twin biobank with DNA from 45,000 twins and blood serum from 15,000 twins, which effectively has also transformed the registry into a powerful resource for molecular studies. We here describe the main projects within which the new collections of both biological samples as well as phenotypic measures have been collected. Coverage by year of birth, zygosity determination, ethnic heterogeneity, and influences of in vitro fertilization are also described.
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| 10. |
- Martin, Cederlöf, 1980-, et al.
(författare)
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The association between childhood autistic traits and adolescent psychotic experiences is explained by general neuropsychiatric problems.
- 2016
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Ingår i: American Journal of Medical Genetics Part B. - Hoboken, USA : Wiley-Blackwell. - 1552-4841 .- 1552-485X. ; 171:2, s. 153-159
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Tidskriftsartikel (refereegranskat)abstract
- Studies suggest associations between childhood autistic traits and adolescent psychotic experiences. However, recent research suggests that a general neuropsychiatric problems factor predicts adverse outcomes better than specific diagnostic entities. To examine if the alleged association between autistic traits and psychotic experiences could rather be explained by a general neuropsychiatric problems factor comprising symptoms of ADHD, tic disorder, developmental coordination disorder, and learning disorder, we conducted a prospective cohort study based on the Child and Adolescent Twin Study in Sweden. In addition, we examined the genetic and environmental influences on the associations. A total of 9,282 twins with data on childhood autistic traits and other neuropsychiatric problems, and follow-up data on psychotic experiences at ages 15 and/or 18 years were included. First, psychotic experiences were regressed on autistic traits and second, the general neuropsychiatric problems factor was added to the model. Auditory hallucinations were analyzed separately from the other psychotic experiences. Finally, twin analyses were employed to disentangle genetic from environmental influences in the observed associations. Replicating prior research, significant associations were found between autistic traits in childhood and auditory hallucinations at ages 15 and 18. However, after controlling for the general neuropsychiatric problems factor, the associations between autistic traits and auditory hallucinations disappeared, whereas the association between the general neuropsychiatric problems factor and auditory hallucinations persisted after controlling for autistic traits. Twin analyses revealed that the association between the general neuropsychiatric problems factor and auditory hallucinations was driven by shared genetic influences. .
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