Publications

Selenium (Se) is an essential trace element in human nutrition, but its role in certain health conditions, particularly among Se sufficient populations, is controversial. A genome-wide association study (GWAS) of blood Se concentrations previously identified a locus at 5q14 near BHMT. We performed a GW meta-analysis of toenail Se concentrations, which reflect a longer duration of exposure than blood Se concentrations, including 4162 European descendants from four US cohorts. Toenail Se was measured using neutron activation analysis. We identified a GW-significant locus at 5q14 (P < 1 × 10(-16)), the same locus identified in the published GWAS of blood Se based on independent cohorts. The lead single-nucleotide polymorphism (SNP) explained ∼1% of the variance in toenail Se concentrations. Using GW-summary statistics from both toenail and blood Se, we observed statistical evidence of polygenic overlap (P < 0.001) and meta-analysis of results from studies of either trait (n = 9639) yielded a second GW-significant locus at 21q22.3, harboring CBS (P < 4 × 10(-8)). Proteins encoded by genes at 5q14 and 21q22.3 function in homocysteine (Hcy) metabolism, and index SNPs for each have previously been associated with betaine and Hcy levels in GWAS. Our findings show evidence of a genetic link between Se and Hcy pathways, both involved in cardiometabolic disease.

Abstract Migraine has an assumed polygenic basis, but the genetic risk variants identified in genome-wide association studies only explain a proportion of the heritability. We aimed to develop machine learning models, capturing non-additive and interactive effects, to address the missing heritability. This was a cross-sectional population-based study of participants in the second and third Trøndelag Health Study. Individuals underwent genome-wide genotyping and were phenotyped based on validated modified criteria of the International Classification of Headache Disorders. Four datasets of increasing number of genetic variants were created using different thresholds of linkage disequilibrium and univariate genome-wide associated p-values. A series of machine learning and deep learning methods were optimized and evaluated. The genotype tools PLINK and LDPred2 were used for polygenic risk scoring. Models were trained on a partition of the dataset and tested in a hold-out set. The area under the receiver operating characteristics curve was used as the primary scoring metric. Classification by machine learning was statistically compared to that of polygenic risk scoring. Finally, we explored the biological functions of the variants unique to the machine learning approach. 43,197 individuals (51% women), with a mean age of 54.6 years, were included in the modelling. A light gradient boosting machine performed best for the three smallest datasets (108, 7,771 and 7,840 variants), all with hold-out test set area under curve at 0.63. A multinomial naïve Bayes model performed best in the largest dataset (140,467 variants) with a hold-out test set area under curve of 0.62. The models were statistically significantly superior to polygenic risk scoring (area under curve 0.52 to 0.59) for all the datasets (p&amp;lt;0.001 to p=0.02). Machine learning identified many of the same genes and pathways identified in genome-wide association studies, but also several unique pathways, mainly related to signal transduction and neurological function. Interestingly, pathways related to botulinum toxins, and pathways related to the calcitonin gene-related peptide receptor also emerged. This study suggests that migraine may follow a non-additive and interactive genetic causal structure, potentially best captured by complex machine learning models. Such structure may be concealed where the data dimensionality (high number of genetic variants) is insufficiently supported by the scale of available data, leaving a misleading impression of purely additive effects. Future machine learning models using substantially larger sample sizes could harness both the additive and the interactive effects, enhancing precision and offering deeper understanding of genetic interactions underlying migraine.

This paper describes the design and characterization of a small, membraneless redox fuel cell. The smallest channel dimensions of the cell were 2 mm × 50 μm or × 200 μm; the cell was fabricated in poly(dimethylsiloxane) using soft lithography. This all-vanadium fuel cell took advantage of laminar flow to obviate the need for a membrane to separate the solutions of oxidizing and reducing components.

Facial pain and other symptoms of temporomandibular disorders (TMD) are rather common in the adult population. According to clinical studies, psychological factors play an important role in the etiology and maintenance of these symptoms. On the other hand, chronic pain can cause depression. The aim of this study was to evaluate the association between symptoms of TMD and depression in a large population sample of young adults. The study was a part of the 31-year follow-up study of the Northern Finland Birth Cohort consisting of 12,058 live births from the year 1966. Questionnaire information concerning TMD symptoms was collected from a subsample of 5,696 subjects. Depression was measured with a question about reported depression (diagnosed by a doctor) and with the Symptom Checklist depression subscale (SCL-25 DS). Of the TMD symptoms, those related to pain had the most significant relations to indicators of depression. In both genders, the proportion of depression indicated with the SCL-25 DS was significantly higher in subjects with pain-related symptoms of TMD, i.e., facial pain and "pain at jaw rest", and in men with "pain on jaw movement", compared with non-pain subjects (p<0.05). Other symptoms of TMD also associated significantly with SCL-25 DS (p>0.05), except "difficulties in mouth opening" among women. Among women, the prevalence of recognized depression was also significantly higher in subjects with pain-related symptoms of TMD, compared with subjects with no pain (p< or =0.05). Almost all the associations remained significant after adjusting for marital status, education, and self-rated general health. In conclusion, the results show that depression has an association with TMD symptoms, especially those related to pain. When treating patients with facial pain, dentists should consider the possible presence of psychopathology and, if necessary, consult appropriate mental health professionals.

The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our "modern" postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.

Background— The impact of overall dietary patterns that reflect actual eating behaviors on mortality caused by cardiovascular or other chronic diseases is largely unknown. Methods and Results— We prospectively evaluated the relation between dietary patterns and risk of cardiovascular, cancer, and all-cause mortality among 72 113 women who were free of myocardial infarction, angina, coronary artery surgery, stroke, diabetes mellitus, or cancer and were followed up from 1984 to 2002. Dietary patterns were derived by factor analysis based on validated food frequency questionnaires administered every 2 to 4 years. Two major dietary patterns were identified: High prudent pattern scores represented high intakes of vegetables, fruit, legumes, fish, poultry, and whole grains, whereas high Western pattern scores reflected high intakes of red meat, processed meat, refined grains, french fries, and sweets/desserts. During 18 years of follow-up, 6011 deaths occurred, including 1154 cardiovascular deaths and 3139 cancer deaths. After multivariable adjustment, the prudent diet was associated with a 28% lower risk of cardiovascular mortality (95% confidence interval [CI], 13 to 40) and a 17% lower risk of all-cause mortality (95% CI, 10 to 24) when the highest quintile was compared with the lowest quintile. In contrast, the Western pattern was associated with a higher risk of mortality from cardiovascular disease (22%; 95% CI, 1 to 48), cancer (16%; 95% CI, 3 to 30), and all causes (21%; 95% CI, 12 to 32). Conclusion— Greater adherence to the prudent pattern may reduce the risk of cardiovascular and total mortality, whereas greater adherence to the Western pattern may increase the risk among initially healthy women.

Journal Article List of Donors to the Library of the Linnean Society Get access Transactions of the Linnean Society of London, Volume os-5, Issue 1, February 1800, Pages 294–296, https://doi.org/10.1111/j.1096-3642.1800.tb00605.x Published: 09 April 2009 Article history Accepted: 22 July 2008 Published: 09 April 2009

We propose that chromosome function is governed by internal mechanical forces generated by programmed tendencies for expansion of the DNA/chromatin fiber against constraining features.

Abstract We aimed to examine the association between the use of metformin and other anti‐diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994–2016) and the NHSII (1995–2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti‐diabetes medications, and other covariates was self‐reported at baseline and repeatedly assessed by follow‐up questionnaires every 2 years. Breast cancer cases were self‐reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person‐years of follow‐up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D ( n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81–1.15) nor other anti‐diabetic medications use (HR = 1.11; 95% CI = 0.90–1.36) associated with significantly lower breast cancer incidence. Among women with T2D ( n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74–1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48–0.94), current use (HR = 1.01; 95% CI = 0.80–1.27) and longer duration of metformin use were not associated with breast cancer (each 2‐year interval: HR = 1.01; 95% CI = 0.95–1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.

Our results suggest that fetal famine exposure is associated with higher blood pressure and an increased risk of hypertension in adulthood. These associations are stronger in participants who have a western dietary pattern or who are overweight as adults.