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The Influence of Rare Genetic Variation in SLC30A8 on Diabetes Incidence and beta-Cell Function

Context/Objective: The variant rs13266634 in SLC30A8, encoding a beta-cell-specific zinc transporter, is associated with type 2 diabetes. We aimed to identify other variants in SLC30A8 that increase diabetes risk and impair beta-cell function, and test whether zinc intake modifies this risk. Design/Outcome: We sequenced exons in SLC30A8 in 380 Diabetes Prevention Program (DPP) participants and ide

Indole-3-propionic acid promotes hepatic stellate cells inactivation

Background & aims: We have previously reported that the serum levels of gut-derived tryptophan metabolite indole-3-propionic acid (IPA) are lower in individuals with liver fibrosis. Now, we explored the transcriptome and DNA methylome associated with serum IPA levels in human liver from obese individuals together with IPA effects on shifting the hepatic stellate cell (HSC) phenotype to inactiv

Iron insight : exploring dietary patterns and iron deficiency among teenage girls in Sweden

PURPOSE: This observational study examined the relationship between self-reported dietary patterns-omnivore, pescatarian, vegetarian, and vegan-and iron status among Swedish teenage girls. Additionally, we compared the consumption of various food groups in relation to iron status.METHODS: Data were collected from 475 female high school students in Malmö and Lund, Sweden, using questionnaires on di

Precision nutrition for cardiometabolic diseases

Precision nutrition is a vibrant and rapidly evolving field of scientific research and innovation with the potential to deliver health, societal and economic benefits by improving healthcare delivery and policies. Advances in deep phenotyping technologies, digital tools and artificial intelligence have made possible early proof-of-concept research that expands the understanding of within- and betw

Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference

Detailed phenotyping is required to deepen our understanding of the biological mechanisms behind genetic associations. In addition, the impact of potentially modifiable risk factors on disease requires analytical frameworks that allow causal inference. Here, we discuss the characteristics of Recall-by-Genotype (RbG) as a study design aimed at addressing both these needs. We describe two broad scen

Gene-lifestyle interplay in type 2 diabetes

Type 2 diabetes (T2D) is widespread, affecting the health of hundreds of millions worldwide. The disease results from the complex interplay of lifestyle factors acting on a backdrop of inherited DNA risk variants. Detecting and understanding biomarkers, whether genotypes or other downstream biological features that dictate a person's phenotypic response to different lifestyle exposures, may have t

Genome-wide and abdominal MRI data provide evidence that a genetically determined favorable adiposity phenotype is characterized by lower ectopic liver fat and lower risk of type 2 diabetes, heart disease, and hypertension

Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits

The Effect of Radioiodine Treatment on TRAb, Anti-TPO, and Anti-TG in Graves' Disease

Background: In Graves' disease (GD), immunocompetent cells infiltrate thyroid tissue with release of TSH-receptor antibodies (TRAb), and radioiodine treatment is known to elicit an immune response with an increase in TRAb. Objectives: The aim was to study if all patients treated with radioiodine respond with a release of TRAb, anti-thyroperoxidase (anti-TPO), and anti-thyroglobulin (anti-TG). Meth

Does pregnancy complication history improve cardiovascular disease risk prediction? : Findings from the HUNT study in Norway

Aim: To evaluate whether history of pregnancy complications [pre-eclampsia, gestational hypertension, preterm delivery, or small for gestational age (SGA)] improves risk prediction for cardiovascular disease (CVD).Methods and results: This population-based, prospective cohort study linked data from the HUNT Study, Medical Birth Registry of Norway, validated hospital records, and Norwegian Cause of

Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and sm

Intact glucose uptake despite deteriorating signaling in adipocytes with high-fat feeding

To capture immediate cellular changes during diet-induced expansion of adipocyte cell volume and number, we characterized mature adipocytes during a short-term high-fat diet (HFD) intervention. Male C57BL6/J mice were fed chow diet, and then switched to HFD for 2, 4, 6 or 14 days. Systemic glucose clearance was assessed by glucose tolerance test. Adipose tissue was dissected for RNA-seq and cell s

Influence of early-life parental severe life events on the risk of type 1 diabetes in children : the DiPiS study

Aims: Stress and severe life events (SLEs) modify autoimmune disease susceptibility. Here, we aimed to establish if SLEs reported by parents during the first 2 years of life influence the risk of developing type 1 diabetes (T1D) using data from the prospective Diabetes Prediction in Skåne (DiPiS) study. Methods: Prospective questionnaire data recorded at 2 months (n = 23,187) and 2 years of age (n

Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci

Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alt

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (valida

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted

Maternal hypertensive disorders of pregnancy and offspring risk of hypertension : a population-based cohort and sibling study

BACKGROUND: Women with a history of hypertensive disorders of pregnancy (HDP) are at increased risk of hypertension, cardiovascular disease, and type 2 diabetes. Offspring from pregnancies complicated by HDP also have worse cardiometabolic status in childhood and young adulthood, but the offspring risk of clinical hypertension in adulthood is largely unknown.METHODS: We studied 13,893 first-born a