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Institute
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the Xchromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10-9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10-9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
Governments have restricted public life during the COVID-19 pandemic, inter alia closing sports facilities and gyms. As regular exercise is essential for health, this study examined the effect of pandemic-related confinements on physical activity (PA) levels. A multinational survey was performed in 14 countries. Times spent in moderate-to-vigorous physical activity (MVPA) as well as in vigorous physical activity only (VPA) were assessed using the Nordic Physical Activity Questionnaire (short form). Data were obtained for leisure and occupational PA pre- and during restrictions. Compliance with PA guidelines was calculated based on the recommendations of the World Health Organization (WHO). In total, n = 13,503 respondents (39 ± 15 years, 59% females) were surveyed. Compared to pre-restrictions, overall self-reported PA declined by 41% (MVPA) and 42.2% (VPA). Reductions were higher for occupational vs. leisure time, young and old vs. middle-aged persons, previously more active vs. less active individuals, but similar between men and women. Compared to pre-pandemic, compliance with WHO guidelines decreased from 80.9% (95% CI: 80.3–81.7) to 62.5% (95% CI: 61.6–63.3). Results suggest PA levels have substantially decreased globally during the COVID-19 pandemic. Key stakeholders should consider strategies to mitigate loss in PA in order to preserve health during the pandemic.
Confinement measures during the COVID-19 pandemic have caused substantial reductions in global physical activity (PA) levels. In view of the manifold health benefits of PA, the development of interventions counteracting this trend is paramount. Our survey with 15,261 participants (38 ± 15 years, 58.5% females) examined preferences towards digital home exercise programs in 14 countries affected by COVID-19. More than two-thirds of the sample (68.4%, n = 10,433) indicated being interested in home exercise, and most participants were willing to work out at least three times per week (89.3%, n = 9328). Binary logistic regression revealed that female sex, working part-time, younger age, and being registered in a gym were associated with willingness to exercise. Flexibility (71.1%, n = 7377), resistance (68.6%, n = 7116), and endurance training (62.4%, n = 6478) were the most preferred types of exercise. Our results may guide health providers in developing individually tailored PA interventions during the current and future pandemics.
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
(2021)
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
