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- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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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.
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| 4. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Fazel, S, et al.
(författare)
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Risk factors for interpersonal violence: an umbrella review of meta-analyses
- 2018
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 213:4, s. 609-614
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Tidskriftsartikel (refereegranskat)abstract
- Interpersonal violence is a leading cause of morbidity and mortality. The strength and population effect of modifiable risk factors for interpersonal violence, and the quality of the research evidence is not known.AimsWe aimed to examine the strength and population effect of modifiable risk factors for interpersonal violence, and the quality and reproducibility of the research evidence.MethodWe conducted an umbrella review of systematic reviews and meta-analyses of risk factors for interpersonal violence. A systematic search was conducted to identify systematic reviews and meta-analyses in general population samples. Effect sizes were extracted, converted into odds ratios and synthesised, and population attributable risk fractions (PAF) were calculated. Quality analyses were performed, including of small study effects, adjustment for confounders and heterogeneity. Secondary analyses for aggression, intimate partner violence and homicide were conducted, and systematic reviews (without meta-analyses) were summarised.ResultsWe identified 22 meta-analyses reporting on risk factors for interpersonal violence. Neuropsychiatric disorders were among the strongest in relative and absolute terms. The neuropsychiatric risk factor that had the largest effect at a population level were substance use disorders, with a PAF of 14.8% (95% CI 9.0–21.6%), and the most important historical factor was witnessing or being a victim of violence in childhood (PAF = 12.2%, 95% CI 6.5–17.4%). There was evidence of small study effects and large heterogeneity.ConclusionsNational strategies for the prevention of interpersonal violence may need to review policies concerning the identification and treatment of modifiable risk factors.Declarations of interestJ.R.G. is an NIHR Senior Investigator. The views expressed within this article are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
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| 7. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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