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Sökning: WFRF:(McGough JJ)

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  • Lee, S. Hong, et al. (författare)
  • Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
  • 2013
  • Ingår i: Nature genetics. - 1546-1718. ; 45:9, s. 984-
  • Tidskriftsartikel (refereegranskat)abstract
    • Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders. © 2013 Nature America, Inc. All rights reserved.
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  • O'Dushlaine, C, et al. (författare)
  • Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
  • 2015
  • Ingår i: Nature neuroscience. - 1546-1726. ; 18:2, s. 199-209
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
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  • Rodriguez, Alina, et al. (författare)
  • Mixed-handedness is linked to mental health problems in children and adolescents
  • 2010
  • Ingår i: Pediatrics. - 0031-4005 .- 1098-4275. ; 125:2, s. E340-E348
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>OBJECTIVE: Problems with language and symptoms of attention-deficit/hyperactivity disorder (ADHD) in childhood and adolescence are often strongly linked to low scholastic performance. Early recognition of children who are at increased risk is necessary. Our objective was to determine whether mixed-handedness, which is associated with atypical cerebral laterality, is associated with language, scholastic, and ADHD symptoms in childhood and adolescence.</p> <p>METHODS: Prospective data come from the Northern Finland Birth Cohort 1986, a longitudinal, population-based birth cohort with assessments when children were 7 to 8 and 16 years of age (N = 7871). Teacher, parent, and/or adolescent reports were used to assess language difficulties, scholastic performance, and mental health, including ADHD symptoms.</p> <p>RESULTS: Mixed-handed children, relative to right-handed, had approximately a twofold increase in odds of having difficulties with language and scholastic performance at the age of 8 years. Eight years later, as 16-year-olds, adolescents had twofold increase in odds concerning difficulties in school with language and with ADHD symptoms. Mixed-handed children were more likely to have scores indicating probable psychiatric disturbance, including ADHD symptoms. As adolescents, mixed-handed children with previous behavioral problems were at considerably higher risk for scoring within the range of probable ADHD-inattention or ADHD-combined case. Mixed-handedness was associated with greater symptom severity in children and adolescents (P = .01) concerning psychiatric disturbance and ADHD inattention but not ADHD hyperactivity.</p> <p>CONCLUSIONS: The results indicate that mixed-handed children have a greater likelihood of having language, scholastic, and mental health problems in childhood and that these persist into adolescence. Thus, these results suggest that mixed-handedness, particularly in the presence of difficulties, could aid in the recognition of children who are at risk for stable problems. Additional research is needed to understand the connections between neural substrates related to atypical cerebral asymmetry, mixed-handedness, and mental health problems including ADHD symptoms.</p>
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9.
  • Rodriguez, Alina, et al. (författare)
  • Mixed-handedness is linked to mental health problems in children and adolescents
  • 2010
  • Ingår i: Pediatrics. - 0031-4005 .- 1098-4275. ; 125:2, s. E340-E348
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>OBJECTIVE: Problems with language and symptoms of attention-deficit/hyperactivity disorder (ADHD) in childhood and adolescence are often strongly linked to low scholastic performance. Early recognition of children who are at increased risk is necessary. Our objective was to determine whether mixed-handedness, which is associated with atypical cerebral laterality, is associated with language, scholastic, and ADHD symptoms in childhood and adolescence.</p><p>METHODS: Prospective data come from the Northern Finland Birth Cohort 1986, a longitudinal, population-based birth cohort with assessments when children were 7 to 8 and 16 years of age (N = 7871). Teacher, parent, and/or adolescent reports were used to assess language difficulties, scholastic performance, and mental health, including ADHD symptoms.</p><p>RESULTS: Mixed-handed children, relative to right-handed, had approximately a twofold increase in odds of having difficulties with language and scholastic performance at the age of 8 years. Eight years later, as 16-year-olds, adolescents had twofold increase in odds concerning difficulties in school with language and with ADHD symptoms. Mixed-handed children were more likely to have scores indicating probable psychiatric disturbance, including ADHD symptoms. As adolescents, mixed-handed children with previous behavioral problems were at considerably higher risk for scoring within the range of probable ADHD-inattention or ADHD-combined case. Mixed-handedness was associated with greater symptom severity in children and adolescents (P = .01) concerning psychiatric disturbance and ADHD inattention but not ADHD hyperactivity.</p><p>CONCLUSIONS: The results indicate that mixed-handed children have a greater likelihood of having language, scholastic, and mental health problems in childhood and that these persist into adolescence. Thus, these results suggest that mixed-handedness, particularly in the presence of difficulties, could aid in the recognition of children who are at risk for stable problems. Additional research is needed to understand the connections between neural substrates related to atypical cerebral asymmetry, mixed-handedness, and mental health problems including ADHD symptoms.</p>
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