Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

https://serval.unil.ch/resource/serval:BIB_1DC9105514C9.P002/REF.pdf

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

https://ir.ymlib.yonsei.ac.kr/bitstream/22282913/165063/1/T999900135.pdf

Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

/pdf/genome-wide-association-study-identifies-eight-loci-3kk2tofyea.pdf

Genome-wide association study identifies eight loci associated with blood pressure

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.

/pdf/a-mega-analysis-of-genome-wide-association-studies-for-major-1gpz4z7d3g.pdf

A mega-analysis of genome-wide association studies for major depressive disorder

Henry Volzke, y Dietrich Alte,1y Carsten Oliver Schmidt, Dorte Radke, Roberto Lorbeer, Nele Friedrich, Nicole Aumann, Katharina Lau, Michael Piontek, Gabriele Born, Christoph Havemann, Till Ittermann, Sabine Schipf, Robin Haring, Sebastian E Baumeister, Henri Wallaschofski, Matthias Nauck, Stephanie Frick, Andreas Arnold, Michael Junger, Julia Mayerle, Matthias Kraft, Markus M Lerch, Marcus Dorr, Thorsten Reffelmann, Klaus Empen, Stephan B Felix, Anne Obst, Beate Koch, Sven Glaser, Ralf Ewert, Ingo Fietze, Thomas Penzel, Martina Doren, Wolfgang Rathmann, Johannes Haerting, Mario Hannemann, Jurgen Ropcke, Ulf Schminke, Clemens Jurgens, Frank Tost, Rainer Rettig, Jan A Kors, Saskia Ungerer, Katrin Hegenscheid, Jens-Peter Kuhn, Julia Kuhn, Norbert Hosten, Ralf Puls, Jorg Henke, Oliver Gloger, Alexander Teumer, Georg Homuth, Uwe Volker, Christian Schwahn, Birte Holtfreter, Ines Polzer, Thomas Kohlmann, Hans J Grabe, Dieter Rosskopf, Heyo K Kroemer, Thomas Kocher, Reiner Biffar,17,y Ulrich John20y and Wolfgang Hoffmann1y

/pdf/cohort-profile-the-study-of-health-in-pomerania-2gw27ug7kr.pdf

Cohort Profile: The Study of Health in Pomerania

Objectives
The reason for the Study of Health in Pomerania (SHIP) is the lack of epidemiological studies with a broad range of health indicators. Furthermore, in Germany there is a need for studies that take into account the particular situation of life after the reunification. One objective of SHIP is to provide prevalence estimates on a broad range of diseases, risk and health factors for a defined region in the former GDR.

Study of Health in Pomerania (SHIP): A health examination survey in an east German region: Objectives and design

A short form of the Fagerström Test for Nicotine Dependence and the Heaviness of Smoking Index in two adult population samples.

The Fagerström test for nicotine dependence in two adult population samples—potential influence of lifetime amount of tobacco smoked on the degree of dependence

Objective: Biomarker distributions must be well known for use as screening tools for hazardous alcohol consumption in general populations The aim of this study was to investigate characteristics of carbohydrate-deficient transferrin (CDT) and to compare it with gamma-glutamyltransferase (GGT) and erythrocyte mean corpuscular volume (MCV) in regard to distribution in the general population; the dose response relationship between alcohol consumption and biomarkers; and the effect of gender, age, body mass index (BMI) and smoking Method: In a cross-sectional health survey in northeast Germany (1997-2001), a sample of 7,008 men and women aged 20-79 years was drawn, following stratification by age and gender Of this sample, 4,310 subjects (2,193 women) took part in the study Alcohol consumption was evaluated by self-reports with a beverage specific quantity-frequency method Results: Biomarker distributions differ across age and gender The distribution of drinkers and nondrinking subjects showed considera

Distribution and dose response of laboratory markers to alcohol consumption in a general population: results of the study of health in Pomerania (SHIP).

C. Adam

Papers

Study of Health in Pomerania (SHIP): A health examination survey in an east German region: Objectives and design

A short form of the Fagerström Test for Nicotine Dependence and the Heaviness of Smoking Index in two adult population samples.

The Fagerström test for nicotine dependence in two adult population samples—potential influence of lifetime amount of tobacco smoked on the degree of dependence

Distribution and dose response of laboratory markers to alcohol consumption in a general population: results of the study of health in Pomerania (SHIP).