Genome-wide association study of preserved ratio impaired spirometry (PRISm).

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV1) <80% predicted and FEV1/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities. METHODS: We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed. RESULTS: 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (rg) between PRISm and spirometric COPD (rg=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (rg=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits. CONCLUSION: This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 (HLX), rs62018863 (TMEM114) and rs185937162 (HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity.

Neuroticism, perceived stress, adverse life events and self-efficacy as predictors of the development of functional somatic disorders: longitudinal population-based study (DanFunD).

BACKGROUND: Functional somatic disorder (FSD) is a unifying diagnosis that includes functional somatic syndromes such as irritable bowel, chronic widespread pain (CWP) and chronic fatigue. Several psychological factors are associated with FSD. However, longitudinal population-based studies elucidating the causal relationship are scarce. AIMS: To explore if neuroticism, perceived stress, adverse life events (ALEs) and self-efficacy can predict the development of FSD over a 5-year period. METHOD: A total of 4288 individuals who participated in the DanFunD baseline and 5-year follow-up investigations were included. FSD was established at both baseline and follow-up, with symptom questionnaires and diagnostic interviews. Neuroticism was measured with the short-form NEO Personality Inventory, perceived stress with the Cohen's Perceived Stress Scale, ALEs with the Danish version of the Cumulative Lifetime Adversity Measure and self-efficacy with the General Self-Efficacy Scale. Associations were investigated with multiple logistic regression models. RESULTS: Perceived stress predicted incident FSD, irritable bowel, CWP and chronic fatigue (odds ratios: 1.04-1.17). Neuroticism predicted incident FSD and chronic fatigue (odds ratios: 1.03-1.16). ALEs predicted incident FSD, CWP and chronic fatigue (odds ratios: 1.06-1.18). An increase in perceived stress from baseline to follow-up was associated with incident FSD, irritable bowel, CWP and chronic fatigue (odds ratios: 1.05-1.22). Contrary, an increase in self-efficacy seemed to be a protective factor (odds ratios: 0.89-0.99). CONCLUSIONS: High neuroticism, high perceived stress and a high number of ALEs are risk factors for the development of FSD. Particularly perceived stress seems to be an important contributor to the onset of FSD.

Factors associated with having previously received a diagnosis of fibromyalgia, chronic fatigue syndrome and irritable bowel syndrome: A cross sectional DanFunD study.

OBJECTIVES: Fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome are highly prevalent conditions and part of the functional somatic syndromes (FSS) diagnosis, that are classified under the unifying umbrella term functional somatic disorder (FSD). Multiple factors are associated with FSD symptom development; However, few studies have explored these associations in relation to the diagnosis status. This study aims to examine associations with a previously received FSS diagnosis from a physician in participants fulfilling the FSD diagnostic criteria in a population-based sample. METHODS: This research employs a comprehensive observational approach using a cross sectional design with data from the DanFunD part two cohort. Information about received FSS diagnoses was obtained from self-reported questionnaires. Participants fulfilling the FSD diagnostic criteria were identified with both self-reported questionnaires and diagnostic interviews. Validated questionnaires were used to assess the examined factors. RESULTS: 1704 cases fulfilled the diagnostic criteria for an FSD according to questionnaires or interviews in the DanFunD study. In participants fulfilling the diagnostic criteria, having previously received an FSS diagnosis by a physician was strongly associated with female sex, negative illness perceptions and poor health-related quality of life for questionnaire and interview-based diagnoses. Less consistent associations were observed for lower socioeconomic status, anxiety, and adverse life events. CONCLUSION: Previously received FSS diagnoses showed associations with multiple factors with a particular strong association with female sex and poor health related quality of life.

Translation and examination of construct validity of the Danish version of the Tampa Scale for Kinesiophobia.

OBJECTIVES: This study investigates the construct validity of the Danish Tampa Scale for Kinesiophobia (TSK). METHODS: The English 17-item scale was translated into Danish adhering to WHO's guidelines. The construct validity of the TSK was examined in a random general population sample of 4,884 18- to 72-year olds with pain within the past 4 weeks. Examination of construct validity adhered to the COSMIN checklist. Structural validity was examined by splitting the sample and conducting exploratory factor analysis on one half and confirmatory factor analysis on the other half. Convergent validity was examined through associations with self-report measures and objective physical performance tests. Reference scores for the TSK were calculated. RESULTS: After translation, all respondents felt confident that they understood the meaning of the items. All but one found the questionnaire acceptable. The exploratory factor analysis suggested that a 1-factor 13-item version without 4 reversed items resulted in the most consistent fit across subgroups of gender, age, and severe pain report. Five different models of the TSK were tested in the confirmatory factor analysis. While none were excellent fits, both one- and two-factor models of the TSK-13 and TSK-11 were acceptable. Two-factor models marginally outperformed one-factor models on goodness of fit. There was no association between TSK scores and muscular fitness or self-reported physical activity. Cardiorespiratory fitness, self-perceived physical fitness, and self-efficacy had weak correlations with TSK scores. Scores showed modest associations with self-report measures of anxiety, illness worry, pain interference, and daily limitations. CONCLUSIONS: Based on an overall consideration of results, we recommend using the TSK-13 as a one-dimensional construct for both research and clinical purposes pending further examinations of the TSK in clinical samples. TSK scores from the present study can serve as a standard of reference for levels of Kinesiophobia in the general population.

COVID-19 vaccination and involuntary movements: A longitudinal panel study.

OBJECTIVE: Despite high COVID-19 vaccination rates in many populations, concerns persist about potential adverse events, including concerns about involuntary movements. While case studies have shown occurrences of involuntary movements following COVID-19 vaccination, no systematic studies have explored this association. Our study aims to investigate the relationship between COVID-19 vaccination and involuntary movements. METHODS: This study employs a longitudinal panel design. The study population consists of 165,834 responses from a total of 97,537 unique individuals sourced from the BiCoVac cohort, which is a randomly sampled cohort of Danish individuals aged 16 to 65. Data were collected through a combination of questionnaires and national registers, and analyses were conducted using mixed effects logistic regression. RESULTS: Vaccinated individuals had lower odds of reporting involuntary movements compared to non-vaccinated individuals. Although adjustments attenuated the results, a consistent pattern of lower odds was observed among the vaccinated individuals. The strongest association for the first dose was observed in individuals who received the vaccine within the last 4 weeks before reporting symptoms (OR = 0.72 (0.60; 0.85)). For the second dose, the strongest association was found in individuals who received the second vaccine dose more than 4 weeks before reporting symptoms (OR = 0.77 (0.65; 0.91)). CONCLUSION: The results of the study do not indicate involuntary movements as an adverse reaction to the COVID-19 vaccine. These findings support the safety profile of the COVID-19 vaccine concerning involuntary movements and contribute to enhancing public trust in vaccination programs.

Is reduced heart rate variability associated with functional somatic disorders? A cross-sectional population-based study; DanFunD.

OBJECTIVES: It has been hypothesised that functional somatic disorders (FSD) could be initiated by sympathetic predominance in the autonomic nervous system as measured by low heart rate variability (HRV). Earlier studies on the association between HRV and FSD are small case-control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study is to assess any associations between HRV and various FSDs and whether chronic stress confounds such an association. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Somatic Disorders conducted 2013-2015 in 10 municipalities in the western part of Greater Copenhagen, Denmark. PARTICIPANTS: A total of 6891 men and women aged 18-72 years were included in the analyses after exclusion of 602 persons with missing HRV data. Various delimitations of FSD (chronic fatigue, chronic widespread pain, irritable bowel and bodily distress syndrome) were identified by validated questionnaires and diagnostic interviews. HRV parameters in time and frequency domains were calculated from successive beat-to-beat heart rate (HR) data using the 'E-motion' HR monitor device during 7 min of supine rest. Chronic stress was assessed by Cohen's self-perceived stress scale. OUTCOME MEASURES: Logistic regression analyses were used to calculate possible associations between the various delimitations of FSD and HRV adjusting for chronic stress. RESULTS: Persons with FSD had a slightly higher mean HR and lower HRV as measured by time domain parameters, whereas associations with frequency domain parameters were not consistent. Adjusting for chronic stress attenuated associations slightly. CONCLUSION: The study supports a sympathetic predominance in persons with FSD, which could not be entirely explained by chronic stress. However, it is not possible to conclude whether the association is a causal factor to or a consequence of FSD.

Lipid metabolism and functional somatic disorders in the general population. The DanFunD study.

OBJECTIVES: Earlier studies on the association between plasma lipid profiles and functional somatic disorders (FSD) are mainly small case control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study was to investigate the associations between various FSDs and plasma lipid profiles (total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides) in a large, unselected population. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Somatic Disorders (DanFunD) conducted in 2011-2015 in 10 municipalities in the western part of greater Copenhagen, Denmark. PARTICIPANTS: A total of 8,608 men and women aged 18-76 years were included in the analyses. Various delimitations of FSD such as chronic fatigue, chronic widespread pain, irritable bowel, and bodily distress syndrome were measured using validated self-administrated questionnaires. Lipid parameters were measured from fasting plasma samples using colorimetric slide methods with Vitros 4600/5600 Ortho Clinical Diagnostics. OUTCOME MEASURES: Logistic regression analyses were used to calculate possible associations between plasma lipids and the various delimitations of FSD. Associations are presented by OR (95% CI) and shown in boxplots. RESULTS: We found a positive association between bodily distress syndrome and triglycerides and non-HDL cholesterol and a negative association with HDL-cholesterol, but no consistent association with total cholesterol. A similar pattern was observed for persons with chronic fatigue, and to some degree for persons with chronic widespread pain, whereas persons with irritable bowel did not show a clear association with the lipid profiles. CONCLUSION: This is the first major study on plasma lipid profiles and FSD indicating an association between some delimitations of FSD and an unfavorable lipid profile. Due to the cross-sectional design, it cannot be determined whether the findings are consequences or determinants of FSD. Further studies-preferable prospective studies-are needed.