Sex-specific genetic architecture of blood pressure.

The genetic and genomic basis of sex differences in blood pressure (BP) traits remain unstudied at scale. Here, we conducted sex-stratified and combined-sex genome-wide association studies of BP traits using the UK Biobank resource, identifying 1,346 previously reported and 29 new BP trait-associated loci. Among associated loci, 412 were female-specific (P ≤ 5 × 10; P > 5 × 10) and 142 were male-specific (P ≤ 5 × 10; P > 5 × 10); these sex-specific loci were enriched for hormone-related transcription factors, in particular, estrogen receptor 1.

Spontaneous coronary artery dissection is infrequent in individuals with heritable thoracic aortic disease despite partially shared genetic susceptibility.

Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD.

Epidemiologic and Genetic Associations of Erythropoietin With Blood Pressure, Hypertension, and Coronary Artery Disease.

[Figure: see text].

Molecular genetic evaluation of pediatric renovascular hypertension due to renal artery stenosis and abdominal aortic coarctation in neurofibromatosis type 1.

The etiology of renal artery stenosis (RAS) and abdominal aortic coarctation (AAC) causing the midaortic syndrome (MAS), often resulting in renovascular hypertension (RVH), remains ill-defined. Neurofibromatosis type 1 (NF-1) is frequently observed in children with RVH. Consecutive pediatric patients (N = 102) presenting with RVH secondary to RAS with and without concurrent AAC were prospectively enrolled in a clinical data base, and blood, saliva and operative tissue, when available, were collected.

An Asian-specific MPL genetic variant alters JAK-STAT signaling and influences platelet count in the population.

Genomic discovery efforts for hematological traits have been successfully conducted through genome-wide association study on samples of predominantly European ancestry. We sought to conduct unbiased genetic discovery for coding variants that influence hematological traits in a Han Chinese population. A total of 5257 Han Chinese subjects from Beijing, China were included in the discovery cohort and analyzed by an Illumina ExomeChip array.

Common variants in signaling transcription-factor-binding sites drive phenotypic variability in red blood cell traits.

Genome-wide association studies identify genomic variants associated with human traits and diseases. Most trait-associated variants are located within cell-type-specific enhancers, but the molecular mechanisms governing phenotypic variation are less well understood. Here, we show that many enhancer variants associated with red blood cell (RBC) traits map to enhancers that are co-bound by lineage-specific master transcription factors (MTFs) and signaling transcription factors (STFs) responsive to extracellular signals.

A Novel Recurrent Genetic Variant Is Associated With a Dysplasia-Associated Arterial Disease Exhibiting Dissections and Fibromuscular Dysplasia.

Objective: While rare variants in the gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined. Approach and Results: We studied 4 independent probands with the pathogenic variant c.

Chromosome 1q21.2 and additional loci influence risk of spontaneous coronary artery dissection and myocardial infarction.

Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic cause of myocardial infarction (MI), typically in young women. We undertook a genome-wide association study of SCAD (N = 270/N = 5,263) and identified and replicated an association of rs12740679 at chromosome 1q21.2 (P = 2.

Rare loss-of-function mutations of PTGIR are enriched in fibromuscular dysplasia.

Aims: Fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. We aimed to identify rare genetic causes to elucidate molecular mechanisms implicated in FMD and SCAD.

PHACTR1 Is a Genetic Susceptibility Locus for Fibromuscular Dysplasia Supporting Its Complex Genetic Pattern of Inheritance.

Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, dissection and aneurysm affecting mainly the renal and cerebrovascular arteries. FMD is often an underdiagnosed cause of hypertension and stroke, has higher prevalence in females (~80%) but its pathophysiology is unclear. We analyzed ~26K common variants (MAF>0.

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese.

Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.

Effects of long-term averaging of quantitative blood pressure traits on the detection of genetic associations.

Blood pressure (BP) is a heritable, quantitative trait with intraindividual variability and susceptibility to measurement error. Genetic studies of BP generally use single-visit measurements and thus cannot remove variability occurring over months or years. We leveraged the idea that averaging BP measured across time would improve phenotypic accuracy and thereby increase statistical power to detect genetic associations.

Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-β expression and connective tissue features.

Fibromuscular dysplasia (FMD) is a rare, nonatherosclerotic arterial disease for which the molecular basis is unknown. We comprehensively studied 47 subjects with FMD, including physical examination, spine magnetic resonance imaging, bone densitometry, and brain magnetic resonance angiography. Inflammatory biomarkers in plasma and transforming growth factor β (TGF-β) cytokines in patient-derived dermal fibroblasts were measured by ELISA.

A gender-specific association of CNV at 6p21.3 with NPC susceptibility.

Copy number variations (CNVs), a major source of human genetic polymorphism, have been suggested to have an important role in genetic susceptibility to common diseases such as cancer, immune diseases and neurological disorders. Nasopharyngeal carcinoma (NPC) is a multifactorial tumor closely associated with genetic background and with a male preponderance over female (3:1). Previous genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) that are associated with NPC susceptibility.