Seismic anisotropy of Precambrian lithosphere : Insights from Rayleigh wave tomography of the eastern Superior Craton

The seismic data used in this study are freely available from the CNDC (Canadian National Data Centre for Earthquake Seismology and Nuclear Explosion Monitoring) and IRIS DMC (Data Management Center) via their data request tools. The Leverhulme Trust (grant RPG-2013-332) and National Science Foundation are acknowledged for financial support. L.P. is supported by Janet Watson Imperial College Department Scholarship and the Romanian Government Research Grant NUCLEU. F.D. is supported by NSERC through the Discovery Grants and Canada Research Chairs program. We also thank two anonymous reviewers and the Associate Editor for insightful comments that helped improve the manuscript.Peer reviewedPublisher PD

Prevalence and risk factors of dry eye in 79,866 participants of the population-based Lifelines cohort study in the Netherlands

Purpose: To investigate the prevalence of dry eye among all adult age categories and to discover independent risk factors by investigating a wide range of etiological categories. Methods: A cross-sectional association study including 79,866 voluntary participants aged 20-94 years of the population-based Lifelines Cohort Study in the Netherlands. Results: Overall, 9.1% of participants had dry eye disease as measured by the Women's Health Study dry eye questionnaire. Prevalence of dry eye symptoms were particularly prevalent in 20-30 years olds. Dry eye was associated with comorbidities in almost all body systems, including musculoskeletal, gastro-intestinal, ophthalmic, autoimmune, psychiatric, pain, functional, dermatological and atopic disorders. Numerous independent risk factors were discovered or confirmed, with strong associations for female sex, contact lens use, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, eye surgery including cataract and laser refractive surgery, keratoconus, osteoarthritis, connective tissue diseases, atherosclerosis, Graves' disease, autistic disorder, depression, 'burnout', Crohn's disease, sarcoid, lichen planus, rosacea, liver cirrhosis, sleep apnea, sinusitis, thyroid function, and air pollution (NO2). High blood pressure and high BMI were strongly associated with less dry eye, as was current smoking, while ex-smokers had more dry eye. No clear link between dry eye and lipid or blood glucose levels was found. Conclusions: This study on dry eye confirmed but also refuted many risk factors from smaller epidemiological studies, and discovered numerous new risk factors in multiple etiological categories. The finding that dry eye symptoms are particularly common in young adults is concerning, and warrants further study

Interaction between the MTHFR C677T polymorphism and traumatic childhood events predicts depression

Childhood trauma is associated with the onset and recurrence of major depressive disorder (MDD). The thermolabile T variant of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) is associated with a limited (oxidative) stress defense. Therefore, C677T MTHFR could be a potential predictor for depressive symptomatology and MDD recurrence in the context of traumatic stress during early life. We investigated the interaction between the C677T MTHFR variant and exposure to traumatic childhood events (TCEs) on MDD recurrence during a 5.5-year follow-up in a discovery sample of 124 patients with recurrent MDD and, in an independent replication sample, on depressive syniptomatology in 665 healthy individuals from the general population. In the discovery sample, Cox regression analysis revealed a significant interaction between MTHFR genotype and TCEs on MOD recurrence (P = 0.017). Over the 5.5-year follow-up period, median time to recurrence was 191 days for T-allele carrying patients who experienced TCEs (T + and TCE +); 461 days for T - and TCE + patients; 773 days for T + and TCE - patients and 866 days for T - and TCE - patients. In the replication sample, a significant interaction was present between the MTHFR genotype and TCEs on depressive symptomatology (P = 0.002). Our results show that the effects of TCEs on the prospectively assessed recurrence of MOD and self-reported depressive symptoms in the general population depend on the MTHFR genotype. In conclusion, T-allele carriers may be at an increased risk for depressive symptoms or MOD recurrence after exposure to childhood trauma

Bivariate genetic modelling of the response to an oral glucose tolerance challenge: A gene x environment interaction approach

AIMS/HYPOTHESIS: Twin and family studies have shown the importance of genetic factors influencing fasting and 2 h glucose and insulin levels. However, the genetics of the physiological response to a glucose load has not been thoroughly investigated. METHODS: We studied 580 monozygotic and 1,937 dizygotic British female twins from the Twins UK Registry. The effects of genetic and environmental factors on fasting and 2 h glucose and insulin levels were estimated using univariate genetic modelling. Bivariate model fitting was used to investigate the glucose and insulin responses to a glucose load, i.e. an OGTT. RESULTS: The genetic effect on fasting and 2 h glucose and insulin levels ranged between 40% and 56% after adjustment for age and BMI. Exposure to a glucose load resulted in the emergence of novel genetic effects on 2 h glucose independent of the fasting level, accounting for about 55% of its heritability. For 2 h insulin, the effect of the same genes that already influenced fasting insulin was amplified by about 30%. CONCLUSIONS/INTERPRETATION: Exposure to a glucose challenge uncovers new genetic variance for glucose and amplifies the effects of genes that already influence the fasting insulin level. Finding the genes acting on 2 h glucose independently of fasting glucose may offer new aetiological insight into the risk of cardiovascular events and death from all causes

The relationship between dry eye and sleep quality

Purpose: Sleep is an important determinant of health and quality of life. This study aimed to clarify the association between dry eye and sleep quality using a large population-based cohort. Methods: 71,761 participants (19-94 yrs, 59.4% female) from the Lifelines cohort in the Netherlands were assessed for dry eye using the Women's Health Study Dry Eye Questionnaire. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was used to examine the relationship between poor sleep quality (PSQI score > 5) and dry eye, while correcting for age, sex, BMI, education, income, and 51 possible confounding comorbidities, including autoimmune diseases and psychiatric disorders. Results: Overall, 8.9% of participants had dry eye. Of these, 36.4% had poor sleep quality compared to 24.8% of controls (OR 1.52 (95%CI 1.44-1.60), P < 0.0001, corrected for age and sex). After correcting for all comorbidities, dry eye was still associated with poor sleep (OR 1.20 (95%CI 1.11-1.28), P < 0.0001). This relationship was seen across all ages and sexes. Patients with dry eye scored worse on all subcomponents of the PSQI. Almost one-in-two (44.9%) persons with dry eye symptoms "often" or "constantly" had poor sleep quality. This proportion was similar to participants with sleep apnea and osteoarthritis. Additionally, increasing symptom frequency was tied to increased prevalence of poor sleep quality. Conclusions: All components of sleep quality were significantly reduced in participants with dry eye, even after correcting for comorbidities. These results indicate the substantial impact of dry eye on patients' lives, especially for those with frequent symptoms

Genetic correlation of exercise with heart rate and respiratory sinus arrhythmia

Purpose: A twin design was used to test whether the association between exercise behavior and heart rate and the association between exercise behavior and respiratory sinus arrhythmia (RSA) derive from a common genetic factor. Methods: Data were available from 157 adolescent (aged 13-22) and 208 middle-aged twin pairs (aged 35-62), divided into five sex by zygosity groups (male and female monozygotic twin pairs, and dizygotic twin pairs of same or opposite sex). Exercise behavior was assessed as the average weekly METs spent on sports activities or other vigorous activities in leisure time (sportMETS) in the last 3 months. RSA and heart period (HP) were assessed in the time domain from the combined ECG and respiration signals. Results: Heritability estimates were 16% and 29% for RSA, 64% and 68% for HP, and 79% and 41% for sportMETS in young and middle-aged twins, respectively. A significant association was found between RSA and sportMETS (0.17) in the adolescent twins that derived entirely from a common genetic factor. No association was found between sportMETS and RSA in the older twins. A significant association was found between HP and sportMETS in both adolescent (0.35) and middle-aged (0.18) twins. A large contribution of common genetic factors to these associations was found amounting to 84% and 88% in the young and middle-aged twins, respectively. Conclusions: Although the results of this study do not preclude causal effects of exercise on RSA and heart rate, they show that the association between exercise and these cardiovascular risk factors largely derives from a common genetic factor

GWASinspector:comprehensive quality control of genome-wide association study results

Quality control (QC) of genome wide association study (GWAS) result files has become increasingly difficult due to advances in genomic technology. The main challenges include continuous increases in the number of polymorphic genetic variants contained in recent GWASs and reference panels, the rising number of cohorts participating in a GWAS consortium, and inclusion of new variant types. Here, we present GWASinspector, a flexible R package for comprehensive QC of GWAS results. This package is compatible with recent imputation reference panels, handles insertion/deletion and multi-allelic variants, provides extensive QC reports and efficiently processes big data files. Reference panels covering three human genome builds (NCBI36, GRCh37 and GRCh38) are available. GWASinspector has a user friendly design and allows easy set-up of the QC pipeline through a configuration file. In addition to checking and reporting on individual files, it can be used in preparation of a meta-analysis by testing for systemic differences between studies and generating cleaned, harmonized GWAS files. Comparison with existing GWAS QC tools shows that the main advantages of GWASinspector are its ability to more effectively deal with insertion/deletion and multi-allelic variants and its relatively low memory use

Medication use and dry eye symptoms:A large, hypothesis-free , population-based study in the Netherlands

Purpose: To date, population-based studies reporting associations between dry eye disease and medications were hypothesis-driven, did not take into account underlying comorbidities, and did not investigate individual drugs. The purpose of this study was to clarify the association of dry eye symptoms with medication classes and in-dividual drugs, using a hypothesis-free approach. Methods: 79,606 participants (age 20-97 years, 59.2% female) from the population-based Lifelines cohort in the Netherlands were cross-sectionally assessed for dry eye symptoms using the Womens' Health Study dry eye questionnaire. All medications used were coded with the ATC classification system. Logistic regression was used to assess the risk of the 59 most-used therapeutic/pharmacological subgroups and the 99 most-used individual drugs (all n > 200) on dry eye symptoms, correcting for age, sex, body mass index, and 48 comorbidities associated with dry eye. Results: Thirty-eight (64%) medication subgroups and fifty-two (53%) individual drugs were associated with dry eye symptoms (P < 0.05), after correction for age and sex only. A multivariable model correcting for comor-bidities revealed highly significant associations between dry eye symptoms and drugs for peptic ulcer (partic-ularly proton pump inhibitors (PPIs)), antiglaucoma and anticholinergic medications. Conclusions: This study underlines that medication use is highly informative of risk of dry eye symptoms. Correction for underlying comorbidities is critical to avoid confounding effects. This study confirms suggested associations between medications and dry eye symptoms at a population level and shows several new associa-tions. The novel link between PPIs and dry eye symptoms deserves particular attention given how commonly they are prescribed

The physical and mental burden of dry eye disease:A large population-based study investigating the relationship with health-related quality of life and its determinants

Purpose: This large cross-sectional population-based study investigated the relationship between dry eye disease (DED) and health-related quality of life (HR-QoL). Methods: Dry eye and HR-QoL were assessed in 78,165 participants (19-94 yrs, 59.2% female) from the Dutch population-based Lifelines cohort, using the WHS and the SF36 questionnaire, respectively. Logistic regression was used to assess the relationship between DED and below median Physical Component Summary (PCS) and Mental Component Summary (MCS) score, corrected for age, sex, education, BMI, and 52 comorbidities. Results: Overall, 8.9% of participants had DED. Participants with DED had an increased risk of low PCS (OR 1.54 (95% CI 1.46-1.62)) and MCS scores (OR 1.39 (95% CI 1.32-1.46)), corrected for age and sex. This risk remained significant after correction for comorbidities (P < 0.0005). Increasing DED symptom frequency was associated with decreasing HR-QoL (P < 0.0005). Undiagnosed DED subjects had a significantly increased risk of low mental HR-QoL with increasing dry eye symptoms compared to diagnosed subjects (P < 0.0005). Compared to allergic conjunctivitis, glaucoma, macular degeneration and retinal detachment, DED showed the highest risk of low HR-QoL. Compared to other common systemic and chronic disorders, such as depression, rheumatoid arthritis, and COPD, DED was distinctive by having a substantial reduction in both PCS and MCS. Conclusion: DED is associated with substantial reductions in both physical and mental HR-QoL, also after correction for associated comorbidities. Not having a diagnosis is associated with worse mental HR-QoL in subjects with severe DED. Our results underline the importance of recognizing dry eye as a serious disorder