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Sökning: WFRF:(Lewis Glyn)

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1.
  • de Jong, Simone, et al. (författare)
  • Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
  • 2018
  • Ingår i: Communications Biology. - Nature Publishing Group. - 2399-3642. ; 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
2.
  • Ripke, Stephan, et al. (författare)
  • A mega-analysis of genome-wide association studies for major depressive disorder
  • 2013
  • Ingår i: Molecular psychiatry. - 1476-5578. ; 18:4, s. 497-511
  • Tidskriftsartikel (refereegranskat)abstract
    • Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.
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3.
  • Andersson, Lena, 1965-, et al. (författare)
  • Can avilability to psychiatric care explain regional differences in disability pension due to psychiatric disorders?
  • 2005
  • Ingår i: Europen Journal of Public Health.
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Background In previous studies we have found regional differences in rates of sick leave and disability pension (DP) with psychiatric diagnosis. Age and sex composition of the populations could not explain these differences. The aim of this study was to more closely study associations between availability of psychiatric health care staff and regional differences in DP due to psychiatric disorders in Norway. Methods The study base was all individuals 16-67 years in Norway (n = 2 668 827 in 2000) and six southern regions in 1990, 1995, 2000. As indicators of psychiatric health care we used numbers of psychiatrists, psychologists and psychiatric nurses/10 000 and numbers of in-patient beds, hospitalization days and numbers of discharges/10 000 in each region. A multiple linear regression model was used for the statistical analysis. Results Regional differences in disability pension with psychiatric diagnoses remained after controlling for availability to psychiatric care. In two semi rural regions the relative risk increased while it decreased in the capitol Oslo after control for availability for psychiatric care. There was an association between the frequency of DP:s and number of psychiatrists and other physicians (RR 1,49 (95%CI 1,37-1,61), psychologists (RR 1,29 (95% CI 1,23-1,36) and associated nurses (RR 0,84, 95%CI 0,80-0,88). No association was found between DP frequency and number of psychiatric nurses (RR 1,03 95% CI 1,00-1,06). Conclusions Incidence rates of DP with psychiatric diagnoses in different regions were associated with the number of psychiatric health care staff. Possible explanations to found positive associations can be an improved identification of psychiatric cases but future studies are needed regarding the role of professional psychiatric staff in vocational rehabilitation.
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4.
  • Bould, Helen, et al. (författare)
  • Parental mental illness and eating disorders in offspring
  • 2015
  • Ingår i: International Journal of Eating Disorders. - 0276-3478. ; 48:4, s. 383-391
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate which parental mental illnesses are associated with eating disorders in their offspring.METHOD: We used data from a record-linkage cohort study of 158,679 children aged 12-24 years at the end of follow-up, resident in Stockholm County from 2001 to 2007, to investigate whether different parental mental illnesses are risk factors for eating disorders in their offspring. The outcome measure was diagnosis of any eating disorder, either from an ICD or DSM-IV code, or inferred from an appointment at a specialist eating disorder clinic.RESULTS: Mental illness in parents is a risk factor for eating disorders in female offspring (Adjusted Hazard Ratio (AHR) 1.57 (95% CI 1.42, 1.92), p &lt; 0.0001). Risk of eating disorders is increased if there is a parental diagnosis of bipolar affective disorder (AHR 2.28 (95% CI 1.39, 3.72), p = 0.004), personality disorder (AHR 1.57 (95% CI 1.01, 2.44), p = 0.043) or anxiety/depression (AHR 1.57 (95% CI 1.32, 1.86), p &lt; 0.0001). There is a lack of statistical evidence for an association with parental schizophrenia (AHR 1.41 (95% CI 0.96, 2.07), p = 0.08), and somatoform disorder (AHR 1.25 (95% CI 0.74, 2.13), p = 0.40). There is no support for a relationship between parental substance misuse and eating disorders in children (AHR 1.08 (95% CI 0.82, 1.43), p = 0.57).DISCUSSION: Parental mental illness, specifically parental anxiety, depression, bipolar affective disorder, and personality disorders, are risk factors for eating disorders in their offspring.
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5.
  • Madrid-Gambin, Francisco, et al. (författare)
  • Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences Evidence From the Avon Longitudinal Study of Parents and Children
  • 2019
  • Ingår i: Biological Psychiatry. - Elsevier. - 0006-3223. ; 86:1, s. 25-34
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The identification of early biomarkers of psychotic experiences (PEs) is of interest because early diagnosis and treatment of those at risk of future disorder is associated with improved outcomes. The current study investigated early lipidomic and coagulation pathway protein signatures of later PEs in subjects from the Avon Longitudinal Study of Parents and Children cohort.METHODS: Plasma of 115 children (12 years of age) who were first identified as experiencing PEs at 18 years of age (48 cases and 67 controls) were assessed through integrated and targeted lipidomics and semitargeted proteomics approaches. We assessed the lipids, lysophosphatidylcholines (n = 11) and phosphatidylcholines (n = 61), and the protein members of the coagulation pathway (n = 22) and integrated these data with complement pathway protein data already available on these subjects.RESULTS: Twelve phosphatidylcholines, four lysophosphatidylcholines, and the coagulation protein plasminogen were altered between the control and PEs groups after correction for multiple comparisons. Lipidomic and proteomic datasets were integrated into a multivariate network displaying a strong relationship between most lipids that were significantly associated with PEs and plasminogen. Finally, an unsupervised clustering approach identified four different clusters, with one of the clusters presenting the highest case-control ratio (p &lt; .01) and associated with a higher concentration of smaller low-density lipoprotein cholesterol particles.CONCLUSIONS: Our findings indicate that the lipidome and proteome of subjects who report PEs at 18 years of age are already altered at 12 years of age, indicating that metabolic dysregulation may contribute to an early vulnerability to PEs and suggesting crosstalk between these lysophosphatidylcholines, phosphatidylcholines, and coagulation and complement proteins.
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8.
  • Zammit, Stanley, et al. (författare)
  • Individuals, Schools, and Neighborhood. A Multilevel Longitudinal Study of Variation in Incidence of Psychotic Disorders
  • 2010
  • Ingår i: Archives of General Psychiatry. ; 67:9, s. 914-922
  • Tidskriftsartikel (refereegranskat)abstract
    • Context Incidence of schizophrenia and other nonaffective psychoses is greater in urban than rural areas, but the reason is unclear. Few studies have examined whether both individual and neighborhood characteristics can explain this association. Furthermore, as has been shown for ethnicity, the effect of individual characteristics may depend on neighborhood context. Objectives To examine (1) whether individual, school, or area characteristics are associated with psychosis and can explain the association with urbanicity and (2) whether effects of individual characteristics on risk of psychosis vary according to school context (reflecting both peer group and neighborhood effects). Design Multilevel longitudinal study of all individuals born in Sweden in 1972 and 1977. Diagnoses were identified through linkage with the Swedish National Patient Register until December 31, 2003. Setting Population-based. Participants A total of 203 829 individuals with data at individual, school, municipality, and county levels. Main Outcome Measures Any nonaffective psychosis, including schizophrenia (881 subjects; 0.43% cumulative incidence). For the study of interactions, the outcome was any psychosis (1944 subjects; 0.95% cumulative incidence). Results Almost all the variance in risk of nonaffective psychosis was explained by individual-level rather than higher-level variation. An association between urbanicity and nonaffective psychosis was explained by higher-level characteristics, primarily school-level social fragmentation. We observed cross-level interactions between individual- and school-level markers of ethnicity, social fragmentation, and deprivation on risk of developing any psychotic disorder, all with qualitative patterns of interaction. Conclusions The association between urbanicity and psychosis appears to be a reflection of increased social fragmentation present within cities. The qualitative interactions observed are consistent with a hypothesis that certain characteristics that define individuals as being different from most other people in their local environment may increase risk of psychosis. These findings have potentially important implications for understanding the etiology of psychotic disorders and for informing social policy.
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