However, PAPP-A modulated the embryo transcriptional profiles by downregulating PPARGC1A and AKR1B1, which are related to lipid metabolism; CASP9, a pro-apoptotic gene; and IFN-τ, a marker of embryo quality (P < 05). Furthermore, the use of PAPP-A improved blastocyst re-expansion in the first 3 h of culture after vitrification (P < 05). Although PAPP-A did not affect the blastocyst lipid content or embryo production, we suggest that embryonic transcriptional modulation could contribute to maintain the balance in embryo lipid metabolism. Furthermore, PAPP-A's approach seems to control key intracellular pathways that improve post-cryopreservation development of blastocysts. biology and enables cardioembolic risk prediction. Atrial fibrillation (AF) is a common cardiac arrhythmia resulting in increased risk of stroke. Despite highly heritable etiology, our understanding of the genetic architecture of AF remains incomplete. Here we performed a genome-wide association study in the Japanese population comprising 9,826 cases among 150,272 individuals and identified East Asian-specific rare variants associated with AF. A cross-ancestry meta-analysis of >1 million individuals, including 77,690 cases, identified 35 new susceptibility loci. Transcriptome-wide association analysis responses. Integrative analysis with ChIP-seq data and functional assessment using human induced pluripotent stem cell-derived cardiomyocytes demonstrated ERRg as having a key role in the transcriptional regulation of AF-associated genes. A polygenic risk score derived from the cross-ancestry meta-analysis predicted increased risks of cardiovascular and stroke mortalities and segregated individuals with cardioembolic stroke in undiagnosed AF patients. Our results provide new biological and clinical insights into AF genetics and suggest their Integrative Medical Sciences, Yokohama, Japan. Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored(1,2). FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 6 × 10(-11)) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants. Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. employee of Patch Biosciences. K.E.: Consultation fees from Sobi, and Orion corporation. A. vitamin d3 benefits : consulting fee from Abbvie, Amgen and Pfizer, lecture fee from Pfizer and Sanofi. H. Jacob: employee of AbbVie. F.R.: employee of AbbVie. B.R.-G.: employee of AbbVie. J.W.: employee of AbbVie. A. Check Details : employee of AstraZeneca. D.S. P.: employee of AstraZeneca. S.P.: employee of AstraZeneca. A. Platt: employee of AstraZeneca. I.T.: employee of AstraZeneca. B.S.: employee of Biogen. C. -Y.C.: employee of Biogen. S.J.: employee of Biogen. H. R.: employee of Biogen. Z.D.: employee of Boehringer Ingelheim. J.-N. J.: employee of Boehringer Ingelheim. M.J.: employee of Boehringer Ingelheim. N.L. : employee of Boehringer Ingelheim. G.O.: employee of Boehringer Ingelheim. S.B.: employee of Bristol Myers Squibb. J. Maranville: employee of Bristol Myers Squibb. R.P.: employee of Bristol Myers Squibb. J.H. : employee of Genentech. R.K.P.: employee of Genentech. M.M. : employee of Genentech. K. Auro: employee of GlaxoSmithKline. M.G.E.: employee of GlaxoSmithKline. D.P.: employee of Research & Development. R.R.G.: employee of Maze Therapeutics. E.M.G.: employee of Maze Therapeutics. S.V.M. : employee of Maze Therapeutics. A.H.-V.: employee of S. Longerich: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., employee of Novartis. C.J.O.: employee of Novartis. M.O.: employee of Novartis. N.R.: employee of Novartis. R.
vitamin d3 benefits|Check Details
