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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

Association of changes in inflammation with variation in glycaemia, insulin resistance and secretion based on the KORA study

Aims: Subclinical systemic inflammation may contribute to the development of type 2 diabetes, but its association with early progression of glycaemic deterioration in persons without diabetes has not been fully investigated. Our primary aim was to assess longitudinal associations of changes in pro-inflammatory (leukocytes, high-sensitivity C-reactive protein (hsCRP)) and anti-inflammatory (adipone

A global overview of precision medicine in type 2 diabetes

The detailed characterization of human biology and behaviors is now possible at scale owing to innovations in biomarkers, bioimaging, and wearable technologies; "big data" from electronic medical records, health insurance databases, and other platforms becoming increasingly accessible; and rapidly evolving computational power and bioinformatics methods. Collectively, these advances are creating un

Disparities in prediabetes and type 2 diabetes prevalence between indigenous and nonindigenous populations from Southeastern Mexico : The Comitan Study

Aims: In this research we assessed the prevalence of prediabetes and type 2 diabetes and its association with social determinants such as indigenous origin and residence area in population from Comitan, Chiapas, Mexico. Methods: The Comitan Study is a population-based study carried out from 2010 to 2012 that included 1844 participants aged ≥ 20 years, 880 indigenous and 964 nonindigenous participa

Revisiting the risk of celiac disease in children born small for gestational age: A sibling design perspective.

Objective: An association between small for gestational age (SGA) and risk for celiac disease (CD) in childhood has previously been reported. However, this association may reflect residual confounding by genetic or environmental factors. For example, presence of subclinical CD in the mother might be a common cause of both SGA and CD in the offspring. We investigate whether SGA is causally associat

Acculturation and celiac disease risk in second-generation immigrants: a nationwide cohort study in Sweden.

Objectives: The burden of celiac disease (CD) is increasingly recognized as a global problem. However, whether this situation depends on genetics or environmental factors is uncertain. The authors examined these aspects in Sweden, a country in which the risk of CD is generally considered to be high. If environmental factors are relevant, CD risk in second-generation immigrant children should be re

Longitudinal assessment of femoral knee cartilage quality using contrast enhanced MRI (dGEMRIC) in patients with anterior cruciate ligament injury - comparison with asymptomatic volunteers.

OBJECTIVE: In this observational longitudinal study we estimate knee joint cartilage glycosaminoglycan (GAG) content, in patients with an acute anterior cruciate ligament (ACL) injury, with or without a concomitant meniscus injury. METHODS: 29 knees (19 men/10 women) were prospectively examined by repeat delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), approximately 3

Sex differences in coeliac disease risk: A Swedish sibling design study.

BACKGROUND: For unknown reasons girls are at an increased risk of coeliac disease compared to boys. However, the observed association might be confounded, since maternal coeliac disease is associated with both an increased risk of the disease in first-degree relatives as well as an increased ratio of girls to boys in offspring. AIMS: We investigate the effect of sex on the risk of coeliac dise

Genetic risk scores ascertained in early adulthood and the prediction of type 2 diabetes later in life.

It is hoped that information garnered from studies on population genetics will one day be translated into a form in which it meaningfully improves the prediction, prevention or treatment of type 2 diabetes. Type 2 diabetes genetics researchers have made extraordinary progress in identifying common genetic variants that are associated with type 2 diabetes, which has shed light on the biological pat