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Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10 '8) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotyp
Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products repor
Aims/hypothesis: There is an extensive body of literature suggesting the involvement of multiple loci in regulating the action of metformin; most findings lack replication, without which distinguishing true-positive from false-positive findings is difficult. To address this, we undertook evidence-based, multiple data integration to determine the validity of published evidence. Methods: We (1) buil
The genome is often the conduit through which environmental exposures convey their effects on health and disease. Whilst not all diseases act by directly perturbing the genome, the phenotypic responses are often genetically determined. Hence, whilst diseases are often defined has having differing degrees of genetic determination, genetic and environmental factors are, with few exceptions, insepara
Objectives To describe the development, implementation and lessons learned of lifestyle intervention to promote appropriate gestational weight gain among Hispanic pregnant women. Design The intervention was informed by an empowerment oriented theoretical framework, and targeted women in the Pregnancy and Early Life Improvement Study. Methods The nutrition component consisted of recommendations for
Type 2 diabetes has become a leading health problem throughout the world. The escalating epidemic of type 2 diabetes is believed to result from a collision between inherent biological susceptibilities (genotypes) and a shift toward dietary habits and lifestyle that promote obesity over the past several decades; the transition from “traditional” to modern “obesogenic” lifestyles is characterized by
Importance: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. Objective: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5 ω-3), docosapentaenoic acid (DPA; 22:5 ω-3), and docosahexaenoic acid (DHA; 22:6 ω-3) an
Falsterbo Peninsula on the south coast of Sweden is low-lying and exposed to flooding. In 1872 the extreme storm surge Backafloden caused large devastation on the Swedish, Danish, and German coasts in the South Baltic Sea. For the Falsterbo Peninsula, the peak storm surge level is estimated to have been 240 cm above normal. If a similar event happened today, the consequences would be far worse, as
OBJECTIVES: Genomewide association studies (GWAS) have identified consistent associations with obesity, with a number of studies implicating eating behavior as a primary mechanism. Few studies have replicated genetic associations with dietary intake. This study evaluates the association between obesity susceptibility loci and dietary intake. METHODS: Data were obtained as part of the Diabetes Prev
Organ-specific autoimmune diseases, such as type 1 diabetes, are believed to result from T-cell-mediated damage of the target tissue. The immune-mediated tissue injury, in turn, is known to depend on complex interactions between genetic and environmental factors. Nevertheless, the mechanisms whereby environmental factors contribute to the pathogenesis of autoimmune diseases remain elusive and repr
Since prenatal glucocorticoids (GC) excess increases the risk of metabolic dysfunctions in the offspring and its effect on β-cell recovery capacity remains unknown we investigated these aspects in offspring from mice treated with dexamethasone (DEX) in the late pregnancy. Half of the pups were treated with streptozotocin (STZ) on the sixth postnatal day (PN). Functional and molecular analyses were
BACKGROUND: Meal-induced metabolic changes trigger an acute inflammatory response, contributing to chronic inflammation and associated diseases. OBJECTIVES: We aimed to characterize variability in postprandial inflammatory responses using traditional (IL-6) and novel [glycoprotein acetylation (GlycA)] biomarkers of inflammation and dissect their biological determinants with a focus on postprandial
Hereditary mechanisms are partially responsible for individual differences in sensitivity to and the preference for sweet taste. The primary aim of this study was to examine the associations between 10 genetic variants and the intake of total sugar, added sugar, and sugars with sweet taste (i.e., monosaccharides and sucrose) in a middle-aged Swedish population. Two single nucleotide polymorphisms
The Covid Symptom Study, a smartphone-based surveillance study on COVID-19 symptoms in the population, is an exemplar of big data citizen science. As of May 23rd, 2021, over 5 million participants have collectively logged over 360 million self-assessment reports since its introduction in March 2020. The success of the Covid Symptom Study creates significant technical challenges around effective da
Background Lifestyle exposures play a major role in the development of disease, yet people vary in their susceptibility. A critical step towards precision medicine is identifying individuals who are resilient or sensitive to the environment, and, assess whether the allocation to these predicted groups are more or less likely to develop cardiometabolic disease.Methods We have used repeated data fro
The present study aims to assess the over-time association of ∼300 lifestyle exposures with nine cardiometabolic traits with the ultimate aim of identifying exposures/exposure groups that could inform lifestyle interventions aiming at controlling cardiometabolic diseases. The analyses were undertaken in a longitudinal sample comprising >31000 adults living in northern Sweden. Linear mixed models w
Evidence of the impact of the COVID-19 pandemic on health behaviours in the general population is limited. In this retrospective longitudinal study including UK and US participants, we collected diet and lifestyle data pre-pandemic (896,286) and peri-pandemic (291,871) using a mobile health app, and we computed a bidirectional health behaviour disruption index. Disruption of health behaviour was h
Metabolism plays a central role in evolution, as resource conservation is a selective pressure for fitness and survival.Resource-driven adaptations offer a good model to study evolutionary innovation more broadly. It remains unknown howresource-driven optimization of genome function integrates chromatin architecture with transcriptional phase transitions.Here we show that tuning of genome architec
Objectives: low vitamin D during pregnancy is common and could adversely affect health outcomes. This study evaluated vitamin D status during pregnancy and early in life, and its association with glucose metabolism. Methods: maternal serum 25(OH)D, glucose, and insulin levels were measured longitudinally during pregnancy in Hispanic women with overweight/ obesity (n = 31) and their infants at birt
Data generated over nearly two decades clearly demonstrate the importance of epigenetic modifications and mechanisms in the pathogenesis of type 2 diabetes. However, the role of pharmacoepigenetics in type 2 diabetes is less well established. The field of pharmacoepigenetics covers epigenetic biomarkers that predict response to therapy, therapy-induced epigenetic alterations as well as epigenetic
