A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P <5 x 10(-8), false discovery rate <0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.Peer reviewe

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Murder, Culture, and Injustice: Four Sensational Cases in American History

Walter Hixson\u27s pithy narrative account of four sensational national murder cases - the Lizzie Borden, Lindbergh baby, Sam Sheppard, and O. J. Simpson trials offers interesting observations into the greater cultural and political forces that shaped their verdicts. His step-by-step analysis of the details of each case provides not only insight by skillful synthesis of the existing literature but also a solid overview of the events surrounding these four cases, each of which became a national obsession as well as a miscarriage of justice. Taking a fresh look at the criminal justice system and the role of the media in the larger American milieu, Hixson delves into sociocultural impacts of crime that are both thought-provoking and fascinating reading. Murder, Culture, and Injustice is a fascinating book. Walter L. Hixson combines an engaging, fast-paced writing style with a thoughtful, well-informed analysis that debunks enduring myths about four of the most celebrated murder cases (and trials) in American history. At the same time, Hixson effectively uses these high-profile cases to explain how social and cultural tensions have sometimes distorted the operation of the legal system, resulting in grotesque miscarriages of justice. Simply put, Murder, Culture, and Injustice is a joy to read. -Jeffrey S. Adler, University of Floridahttps://ideaexchange.uakron.edu/uapress_publications/1057/thumbnail.jp