| 1. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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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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| 2. |
- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 3. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 4. |
- de Jong, E., et al.
(författare)
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Association between sleep duration and overweight : the importance of parenting
- 2012
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Ingår i: International Journal of Obesity. - London : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 36:10, s. 1278-1284
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Sleep duration has been related to overweight in children, but determinants of sleep duration are unclear. The aims were to investigate the association between sleep duration and childhood overweight adjusted for family characteristics and unhealthy behaviours, to explore determinants of sleep duration and to determine with sleep competing activities.METHOD: A cross-sectional study was carried out in 2006 among 4072 children aged 4-13 years in the city of Zwolle, The Netherlands. In these children, data were available on measured height, weight and waist circumference, and from a parental questionnaire, on socio-demographic characteristics, child's sleep duration, nutrition, physical activity and sedentary behaviour. Associations were studied in 2011 using logistic and linear regression analyses, adjusted for potential confounders.RESULTS: Short sleep duration was associated with overweight for 4-8-year-old boys (odds ratio (OR): 3.10; 95% confidence interval (CI): 1.15-8.40), 9-13-year-old boys (OR: 4.96; 95% CI: 1.35-18.16) and 9-13-year-old girls (OR: 4.86; 95% CI: 1.59-14.88). Among 4-8-year-old girls no statistically significant association was found. Determinants for short sleep duration were viewing television during a meal, permission to have candy without asking, not being active with their caregiver and a late bedtime. For all children, short sleep duration was strongly associated with more television viewing and computer use.CONCLUSIONS: Association between sleep duration and overweight is not explained by socio-demographic variables, drinking sugared drinks and eating snacks. Parents have a key role in stimulating optimal sleep duration. Improving parenting skills and knowledge to offer children more structure, and possibly with that, increase sleeping hours, may be promising in prevention of overweight.
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| 5. |
- Ilgunas, Aurelia, et al.
(författare)
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The longitudinal relationship between jaw catching/locking and pain
- 2023
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Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 102:4, s. 383-390
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Tidskriftsartikel (refereegranskat)abstract
- Orofacial pain and joint-related dysfunction can negatively affect daily jaw function. A common cause for limitations in jaw movements is joint-related dysfunction such as various forms of catching and locking. However, knowledge is limited regarding the development and natural course of joint-related jaw dysfunction and its relationship to the onset and course of orofacial pain. Therefore, the aim was to evaluate the incidence, prevalence, and gender differences in jaw catching/locking over time and in relation to orofacial pain in the general population. Data from 3 validated screening questions on orofacial pain and jaw catching/locking were collected from all routine dental checkups in the Public Dental Health Services in Västerbotten, Sweden, from 2010 to 2017. Logistic generalized estimating equation was used to account for repeated observations and Poisson regression for incidence analysis. In total, 180,308 individuals (aged 5–104 y) were screened in 525,707 dental checkups. In 2010, based on 37,647 individuals, the prevalence of self-reported catching/locking was higher in women than in men (3.2% vs. 1.5%; odds ratio, 2.11; 95% confidence interval [CI], 1.83–2.43), and this relationship and magnitude remained similar throughout the study period. The annual incidence rate was 1.1% in women and 0.5% in men. Women were at a higher risk than men for reporting both first onset (incidence rate ratio [IRR], 2.29; 95% CI, 2.11–2.49) and persistent (IRR, 2.31; 95% CI, 2.04–2.63) catching/locking. For the onset subcohort (n = 135,801), an independent onset of orofacial pain or jaw catching/locking exclusively was reported by 84.1%, whereas a concurrent onset was reported by 13.4%. Our findings of higher incidence, prevalence, and persistence in women than in men indicate that the gender differences seen for orofacial pain are evident also for jaw catching/locking. The findings also suggest independent onset of self-reported catching/locking and orofacial pain, which reinforces the pathophysiological differences between these conditions.
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| 6. |
- John, M. T., et al.
(författare)
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Recommendations for use and scoring of oral health impact profile versions
- 2022
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Ingår i: Journal of Evidence-Based Dental Practice. - Philadelphia, PA, United States : Elsevier. - 1532-3382 .- 1532-3390. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: OHIP's original seven-domain structure does not fit empirical data, but a psychometrically sound and clinically more plausible structure with the four OHRQoL dimensions Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact has emerged. Consequently, use and scoring of available OHIP versions need to be revisited. Aim: We assessed how well the overall construct OHRQoL and its four dimensions were measured with several OHIP versions (20, 19, 14, and 5 items) to derive recommendations which instruments should be used and how to score them. Methods: Data came from the “Dimensions of OHRQoL Project” and used the project's learning sample (5,173 prosthodontic patients and general population subjects with 49-item OHIP data). We computed correlations among OHIP versions’ summary scores. Correlations between OHRQoL dimensions, on one hand, and OHIP versions’ domain scores or OHIP-5′s items, on the other hand, were also computed. OHIP use and scoring recommendations were derived for psychometrically solid but also practical OHRQoL assessment. Results: Summary scores of 5-, 14-, 19- and 49-item versions correlated highly (r = 0.91–0.98), suggesting similar OHRQoL construct measurement across versions. The OHRQoL dimensions Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact were best measured by the OHIP domain scores for Physical Disability, Physical Pain, Psychological Discomfort, and Handicap, respectively. Conclusion: Recommendations were derived which OHIP should be preferably used and how OHIP versions should be scored to capture the overall construct and the dimensions of OHRQoL. Psychometrically solid and practical OHRQoL assessment in all settings across all oral health conditions can be achieved with the 5-item OHIP.
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| 7. |
- Lips, E. S., et al.
(författare)
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Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia
- 2012
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 17:10, s. 996-1006
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a highly heritable disorder with a polygenic pattern of inheritance and a population prevalence of similar to 1%. Previous studies have implicated synaptic dysfunction in schizophrenia. We tested the accumulated association of genetic variants in expert-curated synaptic gene groups with schizophrenia in 4673 cases and 4965 healthy controls, using functional gene group analysis. Identifying groups of genes with similar cellular function rather than genes in isolation may have clinical implications for finding additional drug targets. We found that a group of 1026 synaptic genes was significantly associated with the risk of schizophrenia (P = 7.6 x 10(-11)) and more strongly associated than 100 randomly drawn, matched control groups of genetic variants (P < 0.01). Subsequent analysis of synaptic subgroups suggested that the strongest association signals are derived from three synaptic gene groups: intracellular signal transduction (P = 2.0 x 10(-4)), excitability (P = 9.0 x 10(-4)) and cell adhesion and trans-synaptic signaling (P = 2.4 x 10(-3)). These results are consistent with a role of synaptic dysfunction in schizophrenia and imply that impaired intracellular signal transduction in synapses, synaptic excitability and cell adhesion and trans-synaptic signaling play a role in the pathology of schizophrenia. Molecular Psychiatry (2012) 17, 996-1006; doi:10.1038/mp.2011.117; published online 20 September 2011
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| 8. |
- Lövgren, Anna, et al.
(författare)
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Associations between screening for functional jaw disturbances and patient reported outcomes on jaw limitations and oral behaviors
- 2023
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Ingår i: Journal of Evidence-Based Dental Practice. - : Elsevier. - 1532-3382 .- 1532-3390. ; 23:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Temporomandibular disorders (TMDs) is a collective term for pain and functional disturbances related to the jaw muscles and the temporomandibular joint. In contrast to screening for orofacial pain, knowledge is limited on the association between patient-reported outcomes and screening for joint-related functional jaw disturbances. Therefore, our aim was to evaluate the association between a screening question for functional jaw disturbances, and disease-specific outcome measures for functional jaw limitations and oral behaviors.Methods: This study included 299 individuals (201 women; 20-69 years, median 37.0) in a general population sample from Västerbotten, Northern Sweden in 2014. A single screening question for functional jaw disturbances “Does your jaw lock or become stuck once a week or more?” was used to categorize individuals as cases or controls. Patient-reported outcomes on functional jaw disturbances were assessed with the 20-item jaw functional limitation scale (JFLS-20) and oral behaviors with the 21-item Oral Behaviors Checklist (OBC-21).Results: The strongest predictive probability to have a positive screening outcome was functional jaw limitations related to mobility (AUCboot=0.78, 95 CI:0.71-0.86, P <.001), followed by limitations related to communication (AUCboot = 0.74, 95 CI:0.63-0.80, P <.001) and mastication (AUCboot = 0.73, 95 CI:0.66-0.81, P <.001). The frequency of oral behaviors was not significantly associated with a positive screening outcome (AUCboot = 0.65, 95 CI:0.55-0.72, P =.223).Conclusions: Self-reported functional limitations, but not oral behaviors, are strongly associated with a single screening question for frequent functional jaw disturbances. This finding provides support for incorporating a question on jaw catching/locking once a week or more in screening instruments for TMDs.
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| 9. |
- Lövgren, Anna, et al.
(författare)
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Temporomandibular pain and jaw dysfunction at different ages covering the lifespan - A population based study
- 2016
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Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 20:4, s. 532-540
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTemporomandibular pain and jaw dysfunction can have a negative effect on daily life, but these conditions are not well recognized in the health care systems. The general aim was to examine the cross-sectional prevalence of frequent temporomandibular pain and jaw dysfunction in men and women across the lifespan.MethodsThe analysis was based on data from 137,718 individuals (mean age 35years, SD 22.7) who answered three questions (3Q/TMD) included in the digital health declaration in the Public Dental Health care in the county of Vasterbotten, Sweden; Q1: Do you have pain in your temple, face, jaw or jaw joint once a week or more?'; Q2: Does it hurt once a week or more when you open your mouth or chew?'; and Q3: Does your jaw lock or become stuck once a week or more?'ResultsThe prevalence of frequent temporomandibular pain (Q1) was 5.2% among women and 1.8% among men (p<0.0001). The prevalence of frequent pain on jaw movement (Q2) was 2.5% among women and 0.9% among men (p<0.0001). The prevalence of frequent locking of the jaw (Q3) was 2.7% among women and 1.2% among men (p<0.0001).ConclusionsThe study shows that the cross-sectional prevalence of temporomandibular pain and jaw dysfunction varies during the lifespan. For men and women, respectively, symptoms increase during adolescence, peak in middle age and then gradually diminish. The prevalence of these symptoms is significantly higher among women except from the first and last decades of a 100-year lifespan.
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| 10. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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