Correction: Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography.

[This corrects the article DOI: 10.1371/journal.pone.

Type 2 Diabetes risk alleles in Peptidyl-glycine Alpha-amidating Monooxygenase influence GLP-1 levels and response to GLP-1 Receptor Agonists.

Patients with type 2 diabetes vary in their response to currently available therapeutic agents (including GLP-1 receptor agonists) leading to suboptimal glycemic control and increased risk of complications. We show that human carriers of hypomorphic T2D-risk alleles in the gene encoding peptidyl-glycine alpha-amidating monooxygenase as well as -knockout mice, display increased resistance to GLP-1 . inactivation in mice leads to reduced gastric GLP-1R expression and faster gastric emptying: this persists during GLP-1R agonist treatment and is rescued when GLP-1R activity is antagonized, indicating resistance to GLP-1's gastric slowing properties.

14-fold increased prevalence of rare glucokinase gene variant carriers in unselected Danish patients with newly diagnosed type 2 diabetes.

Aims: Rare variants in the glucokinase gene (GCK) cause Maturity-Onset Diabetes of the Young (MODY2/GCK-MODY). We investigated the prevalence of GCK variants, phenotypic characteristics, micro- and macrovascular disease at baseline and follow-up, and treatment among individuals with and without pathogenic GCK variants.

Methods: This is a cross-sectional study in a population-based cohort of 5,433 individuals without diabetes (Inter99 cohort) and in 2,855 patients with a new clinical diagnosis of type 2 diabetes (DD2 cohort) with sequencing of GCK.

Insulin resistance genetic risk score and burden of coronary artery disease in patients referred for coronary angiography.

Aims: Insulin resistance associates with development of metabolic syndrome and risk of cardiovascular disease. The link between insulin resistance and cardiovascular disease is complex and multifactorial. Confirming the genetic link between insulin resistance, type 2 diabetes, and coronary artery disease, as well as the extent of coronary artery disease, is important and may provide better risk stratification for patients at risk.

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.

GLP-1 Receptor Agonist Treatment in Morbid Obesity and Type 2 Diabetes Due to Pathogenic Homozygous Melanocortin-4 Receptor Mutation: A Case Report.

Individuals with obesity due to pathogenic heterozygous () mutations can be treated efficiently with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide. Here, we report the effect of 16 weeks of liraglutide 3 mg/day treatment in a woman with morbid obesity and type 2 diabetes (T2D) due to homozygous pathogenic mutation. The body weight loss was 9.

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses.

Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity.

Context: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity.

Objective: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies.

The influence of transmitted and non-transmitted parental BMI-associated alleles on the risk of overweight in childhood.

Overweight in children is strongly associated with parental body mass index (BMI) and overweight. We assessed parental transmitted and non-transmitted genetic contributions to overweight in children from the Danish National Birth Cohort by constructing genetic risk scores (GRSs) from 941 common genetic variants associated with adult BMI and estimating associations of transmitted maternal/paternal and non-transmitted maternal GRS with child overweight. Maternal and paternal BMI (standard deviation (SD) units) had a strong association with childhood overweight [Odds ratio (OR): 2.

A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity.

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry.

Screening of 31 genes involved in monogenic forms of obesity in 23 Pakistani probands with early-onset childhood obesity: a case report.

Background: Consanguine families display a high degree of homozygosity which increases the risk of family members suffering from autosomal recessive disorders. Thus, homozygous mutations in monogenic obesity genes may be a more frequent cause of childhood obesity in a consanguineous population.

Methods: We identified 23 probands from 23 Pakistani families displaying autosomal recessive obesity.

Sequencing reveals protective and pathogenic effects on development of diabetes of rare GLIS3 variants.

Background: Based on the association of common GLIS3 variants with various forms of diabetes and the biological role of GLIS3 in beta-cells, we sequenced GLIS3 in non-diabetic and diabetic Danes to investigate the effect of rare missense variants on glucose metabolism.

Methods: We sequenced 53 patients with maturity-onset diabetes of the young (MODY), 5,726 non-diabetic participants, 2,930 patients with newly diagnosed type 2 diabetes and 206 patients with glutamic acid decarboxylase antibody (GADA) -positive diabetes.

Results: In total we identified 86 rare (minor allele frequency < 0.

Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetic Determinants of Weight Loss After Bariatric Surgery.

Background: The weight loss after bariatric surgery shows considerable individual variation. Twin studies of response to dietary interventions and studies of bariatric surgery patients suggest that genetic differences may play a role. This study aimed to examine the effect of three genetic risk scores on the inter-individual variation in excess body mass index loss (EBMIL) after Roux-en-Y gastric bypass.

Increased frequency of rare missense PPP1R3B variants among Danish patients with type 2 diabetes.

Background: PPP1R3B has been suggested as a candidate gene for monogenic forms of diabetes as well as type 2 diabetes (T2D) due to its association with glycaemic trait and its biological role in glycogen synthesis.

Objectives: To study if rare missense variants in PPP1R3B increase the risk of maturity onset diabetes of the young (MODY), T2D or affect measures of glucose metabolism.

Method: Targeted resequencing of PPP1R3B was performed in 8,710 samples; MODY patients with unknown etiology (n = 54), newly diagnosed patients with T2D (n = 2,930) and population-based control individuals (n = 5,726, of whom n = 4,569 had normal glucose tolerance).

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits.

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals.

Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography.

Background: Recent GWAS studies have identified more than 300 SNPs associated with variation in blood pressure. We investigated whether a genetic risk score constructed from these variants is associated with burden of coronary heart disease.

Methods: From 2010-2014, 4,809 individuals admitted to coronary angiography in Capital Region of Copenhagen were genotyped.

Genetic Susceptibility for Childhood BMI has no Impact on Weight Loss Following Lifestyle Intervention in Danish Children.

Objective: This study aimed to investigate the effect of a genetic risk score (GRS) comprising 15 single-nucleotide polymorphisms, previously shown to associate with childhood BMI, on the baseline cardiometabolic traits and the response to a lifestyle intervention in Danish children and adolescents.

Methods: Children and adolescents with overweight or obesity (n = 920) and a population-based control sample (n = 698) were recruited. Anthropometric and biochemical measures were obtained at baseline and in a subgroup of children and adolescents with overweight or obesity again after 6 to 24 months of lifestyle intervention (n = 754).

Identification of novel LEPR mutations in Pakistani families with morbid childhood obesity.

Background: Mutations in the genes encoding leptin (LEP), the leptin receptor (LEPR), and the melanocortin 4 receptor (MC4R) are known to cause severe early-onset childhood obesity. The aim of the current study was to examine the prevalence of damaging LEP, LEPR, and MC4R mutations in Pakistani families having a recessive heritance of early-onset obesity.

Methods: Using targeted resequencing, the presence of rare mutations in LEP, LEPR, and MC4R, was investigated in individuals from 25 families suspected of having autosomal recessive early-onset obesity.

Association of alcohol consumption with allergic disease and asthma: a multi-centre Mendelian randomization analysis.

Aims: To use the rs1229984 variant associated with alcohol consumption as an instrument for alcohol consumption to test the causality of the association of alcohol consumption with hay fever, asthma, allergic sensitization and serum total immunoglobulin (Ig)E.

Design: Observational and Mendelian randomization analyses using genetic variants as unbiased markers of exposure to estimate causal effects, subject to certain assumptions.

Setting: Europe.

Brugada Syndrome-Associated Genetic Loci Are Associated With J-Point Elevation and an Increased Risk of Cardiac Arrest.

A previous genome-wide association study found three genetic loci, rs9388451, rs10428132, and rs11708996, to increase the risk of Brugada Syndrome (BrS). Since the effect of these loci in the general population is unknown, we aimed to investigate the effect on electrocardiogram (ECG) parameters and outcomes in the general population. A cohort of 6,161 individuals (median age 45 [interquartile range (IQR) 40-50] years, 49% males), with available digital ECGs, was genotyped and subsequently followed for a median period of 13 [IQR 12.