| 1. |
- Quinn, Patrick D., et al.
(författare)
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Childhood attention-deficit/hyperactivity disorder symptoms and the development of adolescent alcohol problems : A prospective, population-based study of Swedish twins
- 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. 958-970
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Tidskriftsartikel (refereegranskat)abstract
- Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of problematic alcohol and other substance use in adolescence. This study used data from an ongoing, prospective, population-based twin study of Swedish children and adolescents to evaluate the extent to which the association between ADHD symptoms and alcohol problems reflects a unique source of genetic or environmental risk related to ADHD versus a broader predisposition to youth externalizing behavior. We used all available data from same-sex monozygotic (MZ) and dizygotic (DZ) twins on ADHD symptoms in childhood (age 9/12; N = 15,549) and alcohol problems in late adolescence (age 18; N = 2,564). Consistent with prior longitudinal studies, the phenotypic association between hyperactive/impulsive ADHD symptoms and alcohol problems was small in magnitude, whereas the association for inattentive symptoms was even weaker. Additive genetic influences explained 99.8% of the association between hyperactive/impulsive symptoms and alcohol problems. Furthermore, we found that the genetic risk specifically associated with hyperactive/impulsive symptoms was attenuated when estimated in the context of externalizing behavior liability during childhood, of which ADHD symptoms were specific expressions. In sensitivity analyses exploring hyperactivity in mid-adolescence, we found a similar pattern of genetic associations. These results are consistent with previous findings of genetically driven overlap in the etiology of ADHD and problematic alcohol use. At least some of this co-occurrence may result from a general predisposition to externalizing behaviors in youth. © 2015 Wiley Periodicals, Inc.
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| 2. |
- Rydell, Mina, et al.
(författare)
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Genetic and environmental contributions to the association between ADHD and affective problems in early childhood : A Swedish population-based twin study
- 2017
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Ingår i: American Journal of Medical Genetics Part B. - Stockholm : John Wiley & Sons. - 1552-4841 .- 1552-485X. ; 174:5, s. 538-546
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Tidskriftsartikel (refereegranskat)abstract
- Few twin studies have explored the relative contribution of genetic and environmental factors to the association between attention deficit hyperactivity disorder (ADHD) and affective problems, and no study has focused on preschool children. We used the classical twin design to explore the genetic and environmental overlap between ADHD symptoms and affective problems in preschool children, based on 879 five-year-old twin pairs born in Sweden 2004-2005. Questionnaire-based parent-ratings were used to measure ADHD symptoms and affective problems. A bivariate twin design was used to decompose variance in ADHD and affective problems into genetic and environmental components, and to test the degree to which these components overlapped across the two traits. Our results showed that there was a significant correlation of 0.34 (95% Confidence Interval [CI] 0.29-0.38) between ADHD and affective problems. This correlation was mostly explained by additive genetic factors (64%, 95%CI 37-93%), and to a lesser extent by shared environmental factors (35%, 95%CI 10-59%). Nonshared environmental factors did not contribute to the correlation between ADHD and affective problems (0%, 95%CI -9 to 10%). These findings show that there is a significant association between ADHD and affective problems in preschool children that is mostly explained by genetic influences. This adds important knowledge about the etiology of both ADHD and affective problems by indicating that these phenotypes are linked from as early as preschool years. This also needs to be taken into consideration when diagnosing young children and clinicians should consider assessing both affective problems and ADHD if one is present.
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| 3. |
- Agartz, I, et al.
(författare)
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BDNF gene variants and brain morphology in schizophrenia
- 2006
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Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. - : Wiley. - 1552-4841. ; 141B:5, s. 513-523
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Akingbuwa, W. A., et al.
(författare)
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Multivariate analyses of molecular genetic associations between childhood psychopathology and adult mood disorders and related traits
- 2022
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Ingår i: American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 192:1-2, s. 3-12
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitous associations have been detected between different types of childhood psychopathology and polygenic risk scores based on adult psychiatric disorders and related adult outcomes, indicating that genetic factors partly explain the association between childhood psychopathology and adult outcomes. However, these analyses in general do not take into account the correlations between the adult trait and disorder polygenic risk scores. This study aimed to further clarify the influence of genetic factors on associations between childhood psychopathology and adult outcomes by accounting for these correlations. Using a multivariate multivariable regression, we analyzed associations of childhood attention-deficit/hyperactivity disorder (ADHD), internalizing, and social problems, with polygenic scores (PGS) of adult disorders and traits including major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI), derived for 20,539 children aged 8.5-10.5 years. After correcting for correlations between the adult phenotypes, major depression PGS were associated with all three childhood traits, that is, ADHD, internalizing, and social problems. In addition, BMI PGS were associated with ADHD symptoms and social problems, while neuroticism PGS were only associated with internalizing problems and educational attainment PGS were only associated with ADHD symptoms. PGS of bipolar disorder, subjective well-being, and insomnia were not associated with any childhood traits. Our findings suggest that associations between childhood psychopathology and adult traits like insomnia and subjective well-being may be primarily driven by genetic factors that influence adult major depression. Additionally, specific childhood phenotypes are genetically associated with educational attainment, BMI and neuroticism.
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| 5. |
- Alaerts, Maaike, et al.
(författare)
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Detailed analysis of the serotonin transporter gene (SLC6A4) shows no association with bipolar disorder in the Northern Swedish population
- 2009
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Ingår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. - : John Wiley & Sons, Inc. - 1552-4841 .- 1552-485X. ; 150B:4, s. 585-592
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Tidskriftsartikel (refereegranskat)abstract
- Through active reuptake of serotonin into presynaptic neurons, the serotonin transporter (5-HTT) plays an important role in regulating serotonin concentrations in the brain, and it is the site of binding for tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). Therefore it has been hypothesized that this transporter is involved in the etiology of bipolar (BP) disorder. Inconsistent association study results for the SLC6A4 gene encoding 5-HTT reported in literature emphasize the need for more systematic and detailed analyses of this candidate gene. We performed an extensive analysis of SLC6A4 on DNA of 254 BPI patients and 364 control individuals from a Northern Swedish isolated population. This analysis consisted of a HapMap LD-based association study including three widely investigated polymorphisms (5-HTTVNTR, 5-HTTLPR, and rs3813034), a copy-number variation (CNV) analysis and a mutation analysis of the complete coding sequence and the 3'-UTR of SLC6A4. No single marker showed statistically significant association with BPI, nor did any of the haplotypes. In the mutation analysis 13 novel variants were detected, including 2 amino acid substitutions M389V and 1587L, but these are probably not implicated in risk for BP. No deletions or duplications were detected in the CNV analysis. We conclude that variation in the SLC6A4 gene or its regulatory regions does not contribute to the susceptibility for BP disorder in the Northern Swedish population.
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| 6. |
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| 7. |
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| 8. |
- Bena, Frederique, et al.
(författare)
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Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature
- 2013
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Ingår i: American Journal of Medical Genetics Part B. - : Wiley. - 1552-4841 .- 1552-485X. ; 162B:4, s. 388-403
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with NRXN1 exonic deletions described to date and by comprehensively reviewing all comparable copy number variants in all disease cohorts that have been published in the peer reviewed literature (30 separate papers in all). Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%). These showed considerable overlap with previously reported NRXN1-deletion associated phenotypes in terms of both spectrum and frequency. However, we did not find evidence for an association between deletions involving the -isoform of neurexin-1 and increased head size, as was recently published in four cases with a deletion involving the C-terminus of NRXN1. We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The additional rare copy number variants identified may act as possible phenotypic modifiers as suggested in a recent digenic model of neurodevelopmental disorders.
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| 9. |
- Bergen, SE, et al.
(författare)
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National-scale precision medicine for psychiatric disorders in Sweden
- 2018
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Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. - : Wiley. - 1552-485X. ; 177:7, s. 630-634
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Blom, Elin Susanne, et al.
(författare)
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Does APOE explain the linkage of Alzheimer’s disease to chromosome 19q13?
- 2008
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Ingår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-485X. ; 147B:6, s. 778-83
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the impact of the apolipoprotein E gene (APOE) on the chromosome 19 linkage peak from an analysis of sib-pairs affected by Alzheimer's disease. We genotyped 417 affected sib-pairs (ASPs) collected in Sweden and Norway (SWE), the UK and the USA for 10 microsatellite markers on chromosome 19. The highest Zlr (3.28, chromosome-wide P-value 0.036) from the multi-point linkage analysis was located approximately 1 Mb from APOE, at marker D19S178. The linkage to chromosome 19 was well explained by APOE in the whole sample as well as in the UK and USA subsamples, as identity by descent (IBD) increased with the number of epsilon 4 alleles in ASPs. There was a suggestion from the SWE subsample that linkage was higher than would be expected from APOE alone, although the test for this did not reach formal statistical significance. There was also a significant age at onset (aao) effect on linkage to chromosome 19q13 in the whole sample, which manifested itself as increased IBD sharing in relative pairs with lower mean aao. This effect was partially, although not completely, explained by APOE. The aao effect varied considerably between the different subsamples, with most of the effect coming from the UK sample. The other samples showed smaller effects in the same direction, but these were not significant.
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