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Sökning: WFRF:(Mortensen PB)

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  • [1]234567...9Nästa
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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.
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2.
  • Mullins, N., et al. (författare)
  • Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
  • 2021
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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  • Stahl, Eli A, et al. (författare)
  • Genome-wide association study identifies 30 loci associated with bipolar disorder.
  • 2019
  • Ingår i: Nature genetics. - 1546-1718 .- 1061-4036. ; 51:5, s. 793-803
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.
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5.
  • Blokland, G. A. M., et al. (författare)
  • Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
  • 2021
  • Ingår i: Biological Psychiatry. - 0006-3223. ; 91:1, s. 102-117
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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  • Høyerup, P., et al. (författare)
  • Glucagon-like peptide-2 stimulates mucosal microcirculation measured by laser Doppler flowmetry in end-jejunostomy short bowel syndrome patients
  • 2013
  • Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 180:1, s. 12-16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In animal and human studies glucagon-like peptide-2 (GLP-2) has been shown to increase blood flow in the superior mesenteric artery and the portal vein. This study describes the effect of GLP-2 measured directly on the intestinal mucosal blood flow by laser Doppler flowmetry (LDF) in end-jejunostomy short bowel syndrome (SBS) patients. Methods: In five SBS patients with end-jejunostomy a specially designed laser Doppler probe was inserted into the stoma nipple, and blood flow measured directly on the jejunal mucosa for 105. min in relation to no treatment, systemic saline infusion, topical adrenaline application and a subcutaneous injection of 800μg native GLP-2. Results: The GLP-2 injection increased jejunal mucosal blood flow by 79 ± 37% compared to conditions, where no treatment was given (p < 0.001). The significant effect was present at least 105. min. Systemic saline infusion and topical, mucosal adrenaline application did not affect mucosal microcirculation. Conclusions: GLP-2 raises jejunal microcirculation in SBS patients with end-jejunostomy. This may explain the redness and increase in the end-jejunostomy nipple size imminently after commencing GLP-2 injections. The potential beneficial effects of this GLP-2-mediated increase of blood flow in the mesenteric bed should be investigated in clinical conditions other than the short bowel syndrome.
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8.
  • Mullins, Niamh, et al. (författare)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.
  • 2022
  • Ingår i: Biological psychiatry. - 1873-2402. ; 91:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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9.
  • Mustelin, L., et al. (författare)
  • Risk of eating disorders in immigrant populations
  • 2017
  • Ingår i: Acta Psychiatrica Scandinavica. - Stockholm : Wiley-Blackwell. - 0001-690X .- 1600-0447. ; 136:2, s. 156-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The risk of certain psychiatric disorders is elevated among immigrants. To date, no population studies on immigrant health have addressed eating disorders. We examined whether risk of eating disorders in first- and second-generation immigrants differs from native-born Danes and Swedes. Method: All individuals born 1984–2002 (Danish cohort) and 1989–1999 (Swedish cohort) and residing in the respective country on their 10th birthday were included. They were followed up for the development of eating disorders based on out-patient and in-patient data. Results: The risks of all eating disorder types were lower among first-generation immigrants compared to the native populations: Incidence-rate ratio (95% confidence interval) was 0.39 (0.29, 0.51) for anorexia nervosa, 0.60 (0.42, 0.83) for bulimia nervosa, and 0.62 (0.47, 0.79) for other eating disorders in Denmark and 0.27 (0.21, 0.34) for anorexia nervosa, 0.30 (0.18, 0.51) for bulimia nervosa, and 0.39 (0.32, 0.47) for other eating disorders in Sweden. Likewise, second-generation immigrants by both parents were at lower risk, whereas those with only one foreign-born parent were not. Conclusion: The decreased risk of eating disorders among immigrants is opposite to what has been observed for other psychiatric disorders, particularly schizophrenia. Possible explanations include buffering sociocultural factors and underdetection in health care.
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  • Resultat 1-10 av 82
  • [1]234567...9Nästa

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