High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly.

Objective: To establish the prevalence of osteoporosis, vertebral fractures (VFs), and non-VFs in acromegaly patients with long-term controlled disease and factors potentially influencing fracture risk.

Design: Case-control study. Patients and measurements Eighty-nine patients (46% male, mean age: 58 years) were included.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects).

Hundreds of variants clustered in genomic loci and biological pathways affect human height.

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait.

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

Objective: Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin.

Low bone mass in Pompe disease: muscular strength as a predictor of bone mineral density.

Unlabelled: Pompe disease is an inherited metabolic myopathy caused by deficiency of acid alpha-glucosidase. The introduction of enzyme replacement therapy as treatment for the disease may change prospects for patients and may require that more attention be paid to co-morbidities such as osteoporosis.

Methods: Bone mineral status was assessed in children and adults with Pompe disease and compared with reference values by means of dual energy X-ray absorptiometry (DXA) technology (GE Lunar DPX, GE Health Care).

Insulin-resistance and metabolic syndrome are related to executive function in women in a large family-based study.

While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)-levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population.

An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits.

Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits.

New loci associated with kidney function and chronic kidney disease.

Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m(2); n = 5,807 individuals with CKD (cases)).

Interactions between dietary vitamin E intake and SIRT1 genetic variation influence body mass index.

Background: Genetic variation in SIRT1 has been associated with body mass index (BMI) and risk of obesity. SIRT1 may be influenced by diet.

Objective: We studied the gene-diet interaction on BMI at the SIRT1 locus.

The T-13910C polymorphism in the lactase phlorizin hydrolase gene is associated with differences in serum calcium levels and calcium intake.

The C-variant of a T-13910C polymorphism (rs4988235; NT_022135.15:g.25316568G > A) upstream of the lactase phlorizin hydrolase (LPH) gene causes lactose intolerance.

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR.

Genetic architecture of plasma adiponectin overlaps with the genetics of metabolic syndrome-related traits.

Objective: Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome-related traits and the association between these traits and 10 ADIPOQ single nucleotide polymorphisms (SNPs).

Association between type 2 diabetes loci and measures of fatness.

Background: Type 2 diabetes (T2D) is a metabolic disorder characterized by disturbances of carbohydrate, fat and protein metabolism and insulin resistance. The majority of T2D patients are obese and obesity by itself may be a cause of insulin resistance. Our aim was to evaluate whether the recently identified T2D risk alleles are associated with human measures of fatness as characterized with Dual Energy X-ray Absorptiometry (DEXA).

Associations of polymorphisms of eight muscle- or metabolism-related genes with performance in Mount Olympus marathon runners.

Athletic endurance performance is probably partly under genetic control, but genetic association studies have yielded inconclusive results. The objective of the present study was to evaluate the association of polymorphisms in eight muscle- or metabolism-related genes with endurance performance in participants of the Olympus Marathon running race. We recruited 438 athletes who participated in the 2007 and 2008 annual running events of the Olympus Marathon: a 43.

The role of body mass index, insulin, and adiponectin in the relation between fat distribution and bone mineral density.

Despite the positive association between body mass index (BMI) and bone mineral density (BMD) and content (BMC), the role of fat distribution in BMD/BMC remains unclear. We examined relationships between BMD/BMC and various measurements of fat distribution and studied the role of BMI, insulin, and adiponectin in these relations. Using a cross-sectional investigation of 2631 participants from the Erasmus Rucphen Family study, we studied associations between BMD (using dual-energy X-ray absorptiometry (DXA]) at the hip, lumbar spine, total body (BMD and BMC), and fat distribution by the waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and DXA-based trunk-to-leg fat ratio and android-to-gynoid fat ratio.

Menopause impacts the relation of plasma adiponectin levels with the metabolic syndrome.

Objective: Plasma adiponectin is negatively correlated with metabolic syndrome (MetS) components obesity and insulin sensitivity. Here, we set out to evaluate the effect of menopause on the association of plasma adiponectin with MetS.

Design: Data on plasma adiponectin and MetS were available from 2256 individuals participating in the Erasmus Rucphen Family study.

Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture.

Background: Osteoporosis is a highly heritable trait. Many candidate genes have been proposed as being involved in regulating bone mineral density (BMD). Few of these findings have been replicated in independent studies.

Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies.

Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.

SIRT1 genetic variation is related to BMI and risk of obesity.

Objective: SIRT1 has pleiotropic metabolic functions. We investigated whether SIRT1 genetic variation is associated with obesity.

Research Design And Methods: In 6,251 elderly subjects from the prospective, population-based Rotterdam Study, three single nucleotide polymorphisms (SNPs) in the SIRT1 gene were studied in relation to BMI and risk of obesity (BMI > or =30 kg/m(2)) and prospectively with BMI change after 6.

NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium.

Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance.

Osmomediated natriuresis in humans: the role of vasopressin and tubular calcium sensing.

Background: The aim was to investigate the unknown mechanism of osmomediated natriuresis. This is the phenomenon by which hypertonic saline (HS) produces a larger natriuresis than isotonic saline (IS), despite the same sodium content.

Methods: Seven healthy volunteers first received HS and then IS (both 3.

Body composition by dual-energy X-ray absorptiometry in women with previous pre-eclampsia or small-for-gestational-age offspring.

Objective: To investigate differences in body composition and fat distribution between women with previous pre-eclampsia or small-for-gestational-age (SGA) offspring and those with uncomplicated pregnancies.

Design: Cohort study.

Setting: Population-based study in a genetically isolated population in the southwest of the Netherlands.

SIRT1 genetic variation and mortality in type 2 diabetes: interaction with smoking and dietary niacin.

SIRT1 protects cells against oxidative stress and aging. Its activity may be modulated by dietary niacin (vitamin B3) intake. We studied the association of SIRT1 genetic variation with mortality in subjects with increased oxidative stress (type 2 diabetes and smokers) in relation to dietary niacin.