| 11. |
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| 12. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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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| 13. |
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| 14. |
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| 15. |
- Liu, DJ, et al.
(författare)
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Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 369-
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.
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| 16. |
- Schijven, Dick, et al.
(författare)
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Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
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Tidskriftsartikel (refereegranskat)abstract
- Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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| 17. |
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| 18. |
- Wolever, Thomas M S, et al.
(författare)
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Measuring the glycemic index of foods: interlaboratory study.
- 2008
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Ingår i: The American journal of clinical nutrition. - 0002-9165 .- 1938-3207. ; 87:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many laboratories offer glycemic index (GI) services. OBJECTIVE: We assessed the performance of the method used to measure GI. DESIGN: The GI of cheese-puffs and fruit-leather (centrally provided) was measured in 28 laboratories (n=311 subjects) by using the FAO/WHO method. The laboratories reported the results of their calculations and sent the raw data for recalculation centrally. RESULTS: Values for the incremental area under the curve (AUC) reported by 54% of the laboratories differed from central calculations. Because of this and other differences in data analysis, 19% of reported food GI values differed by >5 units from those calculated centrally. GI values in individual subjects were unrelated to age, sex, ethnicity, body mass index, or AUC but were negatively related to within-individual variation (P=0.033) expressed as the CV of the AUC for repeated reference food tests (refCV). The between-laboratory GI values (mean+/-SD) for cheese-puffs and fruit-leather were 74.3+/-10.5 and 33.2+/-7.2, respectively. The mean laboratory GI was related to refCV (P=0.003) and the type of restrictions on alcohol consumption before the test (P=0.006, r2=0.509 for model). The within-laboratory SD of GI was related to refCV (P<0.001), the glucose analysis method (P=0.010), whether glucose measures were duplicated (P=0.008), and restrictions on dinner the night before (P=0.013, r2=0.810 for model). CONCLUSIONS: The between-laboratory SD of the GI values is approximately 9. Standardized data analysis and low within-subject variation (refCV<30%) are required for accuracy. The results suggest that common misconceptions exist about which factors do and do not need to be controlled to improve precision. Controlled studies and cost-benefit analyses are needed to optimize GI methodology. The trial was registered at clinicaltrials.gov as NCT00260858.
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| 19. |
- Kaltsas, G., et al.
(författare)
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THE EFFECT OF PROPHYLACTIC RIGHT HEMICOLECTOMY ON SURVIVAL AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH WELL-DIFFERENTIATED APPENDICEAL NEUROENDOCRINE NEOPLASMS
- 2020
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Ingår i: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 107:Suppl. 2, s. 14-14
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Long-term outcomes, including health-related quality of life (HRQoL) issues are understudied in patients with well-differentiated ppendiceal neuroendocrine neoplasms (WD-ANENs). We aimed to evaluate the validity of currently applied criteria for completion prophylactic right hemicolectomy (pRHC) and determine its association with patient outcomes.Methods: This cohort study included patients with WD-ANENs from five European Centers of Excellence for neuroendocrine tumors. Eligible patients were divided between those who underwent appendectomy alone and those who underwent pRHC. HRQoL EORTCqlqc30 questionnaires and cross-sectional imaging data were prospectively collected.Results: The 166 patients included 119 women (71.2%). Mean age was 31 ± 16 years. Mean follow-up was 51 ± 54 months. Most patients (152[92%]) had tumors≤20 mm. Fifty-eight patients (34.9%) underwent pRHC that was unnecessary in 65.5%(38/58); and in 79.1%(34/43) of tumors≤20 mm. In multivariable analysis, tumor size>20 mm was the only independent predictor for lymph node (LN) positivity(p = 0.021). No disease-specific mortality was reported. Three patients developed recurrence (n = 2inthepRHC group vs. n = 1 in the appendectomy group;p = 0.263). Although global HRQol was not significantly depreciated in patients undergoing pRHC compared to appendectomy alone (median scores 0.79[0.25-1] vs. 0.83[0.08-1], respectively; p = 0.738), impaired social functioning (p = 0.016), diarrhea (p = 0.003) and financial difficulties (0.024) were more frequently reported in the pRHC group. Furthermore, physical-(p = 0.066) and role functioning (p = 0.055), as well as constipation issues(p = 0.072) emerged in the pRHC group with marginal significance.Conclusion: pRHC in WD-ANENs comes at a high rate of unnecessary procedures, functional HRQoL issues and diarrhoea. LN positivity at pRHC may lack prognostic significance, as no disease-specific mortality and scarce recurrence was evident in this series. The validity of contemporary criteria and the value per se of pRHC to patients with WD-ANEN is challenged.
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