[Early life residency associated with the risk of developing type 2 diabetes - the population-based Reykjavík study].

Introduction: Sedentary lifestyle and energy rich food have been associated with the risk of developing type 2 diabetes; limited data are available on environmental conditions in childhood on this risk later in life. The objective was to study if residency in the first 20 years of life affected the risk of developing type 2 diabetes.

Methods: In a cohort of 17811 men (48%) and women, mean age 53 years (range 33-81) participating in the population-based Reykjavík Study from 1967-91, 29% grew up in rural and 35% in coastal areas for an average of 20 years before moving to urban Reykjavík, but 36% lived in Reykjavík from birth.

CRP is associated with lung function decline in men but not women: a prospective study.

Systemic inflammation is associated with impaired lung function. Studies, most cross-sectional, report a stronger association between systemic inflammation and lung function impairment in men than women. The aim was to evaluate gender differences in the longitudinal association between systemic inflammation and lung function.

Heterogeneity in white blood cells has potential to confound DNA methylation measurements.

Epigenetic studies are commonly conducted on DNA from tissue samples. However, tissues are ensembles of cells that may each have their own epigenetic profile, and therefore inter-individual cellular heterogeneity may compromise these studies. Here, we explore the potential for such confounding on DNA methylation measurement outcomes when using DNA from whole blood.

Coronary artery calcium distributions in older persons in the AGES-Reykjavik study.

Coronary Artery Calcium (CAC) is a sign of advanced atherosclerosis and an independent risk factor for cardiac events. Here, we describe CAC-distributions in an unselected aged population and compare modelling methods to characterize CAC-distribution. CAC is difficult to model because it has a skewed and zero inflated distribution with over-dispersion.

Effects of a 6-month multimodal training intervention on retention of functional fitness in older adults: a randomized-controlled cross-over design.

Background: Older adults have the highest rates of disability, functional dependence and use of healthcare resources. Training interventions for older individuals are of special interest where regular physical activity (PA) has many health benefits. The main purpose of this study was to assess the immediate and long-term effects of a 6-month multimodal training intervention (MTI) on functional fitness in old adults.

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations.

Prevalence and prognosis of unrecognized myocardial infarction determined by cardiac magnetic resonance in older adults.

Context: Unrecognized myocardial infarction (MI) is prognostically important. Electrocardiography (ECG) has limited sensitivity for detecting unrecognized MI (UMI).

Objective: Determine prevalence and mortality risk for UMI detected by cardiac magnetic resonance (CMR) imaging or ECG among older individuals.

[A study of risk factors for cardiovascular disease among schizophrenic patients using the rehabilitation mental health services at Kleppur].

Background: Studies have shown that schizophrenic patients die on average 15-20 years earlier than the normal population, and that increased prevalance of cardiovascular risk factors plays a crucial role Schizophrenic patients are underdiagnosed and undertreated when it comes to diabetes, hypertension and dyslipidemia. The aim of this study was to investigate the prevalence of metabolic syndrome, obesity, hypertension, diabetes and dyslipidemia among schizophrenic patients in Iceland.

Methods: An observational study of 106 schizophrenic patients in Iceland during the period 2007-2009.

Persistence of the effect of birth size on dysglycaemia and type 2 diabetes in old age: AGES-Reykjavik Study.

We studied the effect of birth size on glucose and insulin metabolism among old non-diabetic individuals. We also explored the combined effect of birth size and midlife body mass index (BMI) on type 2 diabetes in old age. Our study comprised 1,682 Icelanders whose birth records included anthropometrical data.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale.

Rye bread consumption in early life and reduced risk of advanced prostate cancer.

Objective: To determine whether consumption of whole-grain rye bread, oatmeal, and whole-wheat bread, during different periods of life, is associated with risk of prostate cancer (PCa).

Methods: From 2002 to 2006, 2,268 men, aged 67-96 years, reported their dietary habits in the AGES-Reykjavik cohort study. Dietary habits were assessed for early life, midlife, and current life using a validated food frequency questionnaire.

Genome-wide association and functional follow-up reveals new loci for kidney function.

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80.

Mid-thigh cortical bone structural parameters, muscle mass and strength, and association with lower limb fractures in older men and women (AGES-Reykjavik Study).

In a cross-sectional study we investigated the relationship between muscle and bone parameters in the mid-thigh in older people using data from a single axial computed tomographic section through the mid-thigh. Additionally, we studied the association of these variables with incident low-trauma lower limb fractures. A total of 3,762 older individuals (1,838 men and 1,924 women), aged 66-96 years, participants in the AGES-Reykjavik study, were studied.

Effect of vertebral fractures on function, quality of life and hospitalisation the AGES-Reykjavik study.

Background: understanding the determinants of health burden after a fracture in ageing populations is important.

Objective: assess the effect of clinical vertebral and other osteoporotic fractures on function and the subsequent risk of hospitalisation.

Design: individuals from the prospective population-based cohort study Age, Gene/Environment Susceptibility (AGES)-Reykjavik study were examined between 2002 and 2006 and followed up for 5.

The use of digital photographs for the diagnosis of hand osteoarthritis: the AGES-Reykjavik study.

Background: The objective of the study was to standardize a method using digital photographs to diagnose and grade hand osteoarthritis (HOA), to compare it with radiographs and clinical examination with regard to prevalence and relation to symptoms, and finally to construct a simple shortened version suitable for use in very large studies, where a global estimate may be preferable.

Methods: High quality photographs with standard distance and hand positioning were analysed for the presence of HOA and subsequently compared with standard radiographs and clinical examination in 381 random participants in the AGES-Reykjavik Study, a large population study. The mean age of the participants was 76 years.

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)).

Milk intake in early life and risk of advanced prostate cancer.

The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002-2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life.

Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.

Background: Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI.

Methods And Results: Computed tomography was used to assess quantity of CAC.

Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility--Reykjavik Study (AGES-R).

Aims/hypothesis: We aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus.

Methods: The study population consisted of 4,994 persons aged ≥ 67 years, who participated in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-R). Type 2 diabetes mellitus was defined as HbA(1c) ≥ 6.

Brain tissue volumes in the general population of the elderly: the AGES-Reykjavik study.

Imaging studies have reported conflicting findings on how brain structure differs with age and sex. This may be explained by discrepancies and limitations in study population and study design. We report a study on brain tissue volumes in one of the largest cohorts of individuals studied to date of subjects with high mean age (mean ± standard deviation (SD) 76 ± 6 years).

Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility--Reykjavik study.

Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear.

Common genetic variation in the 3'-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium.

Background: Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events.

Methods And Results: We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants.