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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

Association between paternal smoking at the time of pregnancy and the semen quality in sons

BACKGROUND: Maternal smoking during pregnancy has repeatedly been associated with decreased sperm counts in sons. Nevertheless, our team recently detected a lower total sperm count in the sons of smoking fathers as compared to sons of non-smoking fathers. Since paternal and maternal tobacco smoking often coincide, it is difficult to discriminate whether effects are mediated paternally or maternall

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

Postpregnancy BMI in the Progression From Hypertensive Disorders of Pregnancy to Type 2 Diabetes

OBJECTIVE: To study the extent to which BMI after pregnancy adds to the elevated risk of postpregnancy type 2 diabetes in women with a history of hypertensive disorders of pregnancy (HDP) (preeclampsia or gestational hypertension).RESEARCH DESIGN AND METHODS: We used data from the Nurses' Health Study II, a prospective cohort study. In women aged 45-54 years without prior gestational diabetes mell

Brain volumes and developmental outcome in childhood following fetal growth restriction leading to very preterm birth

Background: Children born very preterm (PT) after fetal growth restriction (FGR) exhibit cognitive impairment at early school age. The relationship between neurodevelopmental impairment and attained regional brain volumes is unknown. Methods: We studied 23 preterm children with FGR (PT-FGR), 24 matched preterm children AGA (PT-AGA), and 27 matched term AGA children (T-AGA) by measuring brain volum

Motivations for data sharing—views of research participants from four European countries : A DIRECT study

The purpose of this study was to explore and compare different countries in what motivated research participants’ decisions whether to share their de-identified data. We investigated European DIRECT (Diabetes Research on Patient Stratification) research project participants’ desire for control over sharing different types of their de-identified data, and with who data could be shared in the future

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Braz

Nature vs nurture in knee osteoarthritis – the importance of age, sex and body mass index

Objective: (1) To estimate the life-time genetic contribution for knee osteoarthritis (OA) surgery and (2) to explore any differences in the genetic contribution across age, sex and body mass index (BMI). Methods: We studied the sex-specific genetic contribution to knee OA surgery in a prospective cohort study of 62,490 twins aged 35 years or older with a follow-up period of up to 47 years (10,092

Genotype-Based Recall Studies in Complex Cardiometabolic Traits

In genotype-based recall (GBR) studies, people (or their biological samples) who carry genotypes of special interest for a given hypothesis test are recalled from a larger cohort (or biobank) for more detailed investigations. There are several GBR study designs that offer a range of powerful options to elucidate (1) genotype-phenotype associations (by increasing the efficiency of genetic associati

Long-term follow-up of patients undergoing standardized bicycle exercise stress testing : new recommendations for grading of exercise capacity are clinically relevant

Introduction: A new grading of exercise capacity during bicycle stress testing has been proposed in Sweden based on the new reference material (‘the Kalmar material’), which has not been validated. We aimed to examine the prognostic information of the new grading of exercise capacity during exercise stress testing. Methods: Data on all bicycle exercise tests performed at the Department of Clinical

Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors

Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies

Co-afflicted but invisible : A qualitative study of perceptions among informal caregivers in cancer care

This article explores the lived experience of informal caregivers in cancer care, focusing on the perceived burden and needs of individuals seeking support from an informal group for next of kin. A total of 28 individuals who were closely related to a patient with cancer participated in focus group interviews. Three themes were identified: setting aside one’s own needs, assuming the role of projec

Variation in the plasma membrane monoamine transporter (PMAT) (encoded by SLC29A4) and organic cation transporter 1 (OCT1) (encoded by SLC22A1) and gastrointestinal intolerance to metformin in type 2 diabetes : An IMI direct study

OBJECTIVE Gastrointestinal adverse effects occur in 20–30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5–10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transport

Echocardiographic Findings in Patients with Mild to Moderate Chronic Kidney Disease without Symptomatic Heart Failure : A Population-Based Study

BACKGROUND: Renal dysfunction is an established risk factor for cardiovascular disease, but early disease states in both organs are poorly studied.OBJECTIVE: This cross-sectional population-based study aims to investigate if there is an early association between kidney function and echocardiographic markers of cardiac structure and diastolic function.METHODS: The study population consisted of 1,50

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies

Clinical validation of the Swedish version of Dyspnoea-12 instrument in outpatients with cardiorespiratory disease

Introduction Breathlessness is the cardinal symptom in both cardiac and respiratory diseases, and includes multiple dimensions. The multidimensional instrument Dyspnoea-12 has been developed to assess both physical and affective components of breathlessness. This study aimed to perform a clinical validation of the Swedish version of Dyspnoea-12 in outpatients with cardiorespiratory disease. Method

Validation of the Swedish Multidimensional Dyspnea Profile (MDP) in outpatients with cardiorespiratory disease

Introduction Breathlessness is a cardinal symptom in cardiorespiratory disease. An instrument for measuring different aspects of breathlessness was recently developed, the Multidimensional Dyspnea Profile (MDP). This study aimed to validate the MDP in terms of the underlying factor structure, internal consistency, test-retest reliability and concurrent validity in Swedish outpatients with cardiore