RESUMEN
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Herencia Multifactorial/genética , Femenino , Redes Reguladoras de Genes/genética , Estudio de Asociación del Genoma Completo/métodos , Hematopoyesis/genética , Humanos , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
BACKGROUND: The use of calcium supplements to prevent declines in bone mineral density and fractures is widespread in the United States, and thus reports of elevated cardiovascular disease (CVD) risk in users of calcium supplements are a major public health concern. Any elevation in CVD risk with calcium supplement use would be of particular concern in individuals with type 2 diabetes (T2D) because of increased risks of CVD and fractures observed in this population. OBJECTIVE: In this study, we examined associations between calcium intake from diet and supplements and measures of subclinical CVD (calcified plaque in the coronary artery, carotid artery, and abdominal aorta) and mortality in individuals affected by T2D. DESIGN: We performed a cross-sectional analysis in individuals affected by T2D from the family-based Diabetes Heart Study (n = 720). RESULTS: We observed no significant associations of calcium from diet or supplements with any of our measures of calcified plaque, and no greater mortality risk was observed with increased calcium intake. Instead, calcium supplement use was modestly associated with reduced all-cause mortality in women (HR: 0.62; 95% CI: 0.42, 0.92; P = 0.017). CONCLUSION: Our results do not support a substantial association between calcium intake from diet or supplements and CVD risk in individuals with T2D.