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  • The impact of anorexia nervosa and obesity polygenic risk on childhood growth: a 20-year longitudinal population-based study
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-16
    Mohamed Abdulkadir; Christopher Huebel; Moritz Herle; Ruth Loos; Gerome Breen; Cynthia Bulik; Nadia Micali

    Background: Deviating growth from the norm during childhood has been associated with anorexia nervosa (AN) and obesity later in life. In this study, we examined whether polygenic scores (PGS) for AN and obesity are associated, individually or combined, with a range of anthropometric trajectories spanning the first two decades of life. Methods: AN-PGS and obesity-PGS were calculated for participants

    更新日期:2020-10-17
  • Effect of APOE and a polygenic risk score on incident dementia and cognitive decline in a healthy older population
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-16
    Moeen Riaz; Aamira Huq; Joanne Ryan; Suzanne G Orchard; Jane Tiller; Jessica Lockery; Robyn L Woods; Rory Wolfe; Alan E Renton; Alison M. Goate; Robert Sebra; Eric Schadt; Amy Brodtmann; Raj C Shah; Elsdon Storey; Anne M Murray; John J McNeil; Paul Lacaze

    Importance: Few studies have measured the effect of genetic factors on dementia and cognitive decline in a population of healthy older individuals followed prospectively. Objective: To examine the effect of Apolipoprotein E (APOE) genotypes and a polygenic risk score (PRS) on incident dementia and cognitive decline in a longitudinal cohort of healthy older people. Design, Setting and Participants:

    更新日期:2020-10-17
  • Circulating Proteins Influencing COVID-19 Susceptibility and Severity: a Mendelian Randomization Study
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-14
    Sirui Zhou; Guillaume Butler-Laporte; Tomoko Nakanishi; David Morrison; Jonathan Afilalo; Marc Afilalo; Nofar Kimchi; Zaman Afrasiabi; Nardin Rezk; Meriem Bouab; Charlotte Guzman; Louis Petitjean; Xioaqing Xue; Christos Tselios; Branka Vulesevic; Yiheng Chen; Vincent Mooser; Vincenzo Forgetta; Daniel Kaufmann; Brent Richards

    Proteins detectable in peripheral blood may influence COVID-19 susceptibility or severity. However, understanding which circulating proteins are etiologically involved is difficult because their levels may be influenced by COVID-19 itself and also subject to confounding factors. To identify circulating proteins influencing COVID-19 susceptibility and severity we undertook a large-scale two-sample Mendelian

    更新日期:2020-10-15
  • Genetics of Low Polygenic Risk Score Type 1 Diabetes Patients: rare variants in 22 novel loci
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-14
    Jingchun Qu; Huiqi Qu; Jonathan Bradfield; Joseph Glessner; Xiao Chang; Lifeng Tian; Michael March; Jeffrey D Roizen; Patrick Sleiman; Hakon Hakonarson

    With polygenic risk score (PRS) for autoimmune type 1 diabetes (T1D), this study identified T1D cases with low T1D PRS and searched for susceptibility loci in these cases. Our hypothesis is that genetic effects (likely mediated by relatively rare genetic variants) of non-mainstream (or non-autoimmune) T1D might have been diluted in the previous studies on T1D cases in general. Two cohorts for the PRS

    更新日期:2020-10-15
  • Whole genome sequencing delineates regulatory and novel genic variants in childhood cardiomyopathy
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-14
    Robert Lesurf; Abdelrahman Said; Oyediran Akinrinade; Jeroen Breckpot; Kathleen Delfosse; Ting Liu; Roderick Yao; Fintan McKenna; Ramil R Noche; Winona Oliveros; Kaia Mattioli; Anastasia Miron; Qian Yang; Guoliang Meng; Michelle Chan Seng Yue; Wilson WL Sung; Bhooma Thiruvahindrapuram; Genomics England Research Consortium; Jane Lougheed; Erwin Oechslin; Lynn Bergin; John Smythe; Tapas Mondal; Marta

    Cardiomyopathy (CMP) is a heritable genetic disorder. Protein-coding variants account for 20 to 30 percent of cases. The contribution of variants in noncoding DNA elements that regulate gene expression has not been explored. We performed whole genome sequencing (WGS) of 228 unrelated CMP families. Besides pathogenic protein coding variants in known CMP genes, 5% cases harbored rare loss of function

    更新日期:2020-10-15
  • Genome-wide association study identifies five risk loci for pernicious anemia and implicates the role of HLA-DR15 haplotype
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-14
    Triin Laisk; Maarja Lepamets; Reedik Mägi

    Pernicious anemia is a rare condition characterized by vitamin B12 deficiency anemia due to lack of intrinsic factor, often caused by autoimmune gastritis. Patients with pernicious anemia have a higher incidence of other autoimmune disorders, such as type 1 diabetes, vitiligo and autoimmune thyroid issues. Therefore, the disease has a clear autoimmune basis, although the genetic susceptibility factors

    更新日期:2020-10-15
  • Genetic correlation and causality of cancers and Parkinson′s disease
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-12
    Konstantin Senkevich; Sara Bandres Ciga; Eric Yu; Upekha E Liyanage; International Parkinson Disease Genomics Consortium (IPDGC); Alastair J Noyce; Ziv Gan-Or

    Background and objectives: Most cancers appear with reduced frequency in Parkinson ′ s disease (PD), but the prevalence of melanoma and brain cancers are often reported to be increased. Shared genetic architecture and causal relationships to explain these associations have not been fully explored. Methods: Linkage disequilibrium score regression (LDSC) was applied for five cancer studies with available

    更新日期:2020-10-12
  • A Phase 1b/2a Clinical Trial of Dantrolene Sodium in Patients with Wolfram Syndrome
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-12
    Damien Abreu; Stephen I Stone; Toni Pearson; Robert Bucelli; Ashley N Simpson; Stacy Hurst; Cris M Brown; Kelly Kries; Hongjie Gu; James Hoekel; Lawrence Tychsen; Gregory P Van Stavern; Neil H White; Bess A Marshall; Tamara Hershey; Fumihiko Urano

    Background. Wolfram syndrome is a rare endoplasmic reticulum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Although there is currently no treatment to delay, halt, or reverse the progression of Wolfram syndrome, preclinical studies in cell and rodent models suggest that therapeutic strategies targeting endoplasmic reticulum calcium

    更新日期:2020-10-12
  • Novel Aggregative trans-eQTL Association Analysis of Known Genetic Variants Detect Trait-specific Target Gene-sets
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-06
    Diptavo Dutta; Yuan He; Ashis Saha; Marios Arvanitis; Alexis Battle; Nilanjan Chatterjee

    Large scale genetic association studies have identified many trait-associated variants and understanding the role of these variants in downstream regulation of gene-expressions can uncover important mediating biological mechanisms. In this study, we propose Aggregative tRans assoCiation to detect pHenotype specIfic gEne-sets (ARCHIE), as a method to establish links between sets of known genetic variants

    更新日期:2020-10-07
  • Whole Genome Sequencing identifies novel structural variant in a large Indian family affected with X - linked agammaglobulinemia
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-06
    Abhinav Jain; Geeta Madathil Govindaraj; Athulya Edavazhippurath; Nabeel Faisal; Rahul C Bhoyar; Vishu Gupta; Ramya Uppuluri; Shiny Padinjare Manakkad; Atul Kashyap; Anoop Kumar; Mohit Kumar Divakar; Mohamed Imran; Sneha Sawant; Aparna Dalvi; Krishnan Chakyar; Manisha Madkaikar; Revathi Raj; Sridhar Sivasubbu; Vinod Scaria

    Background X - linked agammaglobulinemia (XLA, OMIM #300755) is a primary immunodeficiency disorder caused by pathogenic variations in the BTK gene, characterized by failure of development and maturation of B lymphocytes. The estimated prevalence worldwide is 1 in 190,000 male births. Recently, genome sequencing has been widely used in difficult to diagnose and familial cases. We report a large Indian

    更新日期:2020-10-06
  • An artificial neural network approach integrating plasma proteomics and genetic data identifies PLXNA4 as a new susceptibility locus for pulmonary embolism.
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-06
    Misbah Razzaq; MariaJesus Iglesias; Manal Ibrahim; Louisa Goumidi; Omar Soukarieh; Carole Proust; Maguelonne Roux; Pierre Suchon; Anne Boland; Delphine Daiain; Robert Olaso; Lynn Butler; Jean Francois Deleuze; Jacob Odeberg; Pierre-Emmanuel Morange; David Alexandre Tregouet

    Venous thromboembolism is the third common cardiovascular disease and is composed of two entities, deep vein thrombosis (DVT) and its fatal form, pulmonary embolism (PE). While PE is observed in ~40% of patients with documented DVT, there is limited biomarkers that can help identifying patients at high PE risk. To fill this need, we implemented a two hidden-layers artificial neural networks (ANN) on

    更新日期:2020-10-06
  • Multi-omics highlights ABO plasma protein as a causal risk factor for COVID-19
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-06
    Ana I Hernandez Cordero; Xuan Li; Stephen Milne; Chen Xi Yang; Yohan Bosse; Philippe Joubert; Wim Timens; Maarten van den Berge; David Nickle; Ke Hao; Don D Sin

    SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) and the current health crisis. Despite intensive research efforts, the genes and pathways that contribute to COVID-19 remain poorly understood. We therefore used an integrative genomics (IG) approach to identify candidate genes responsible for COVID-19 and its severity. We used Bayesian colocalization (COLOC) and summary-based Mendelian

    更新日期:2020-10-06
  • LTA4H association with montelukast response in early and late-onset asthma
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-06
    Cyrielle Maroteau; Antonio Espuela Ortiz; Esther Herrera Luis; Sundararajan Srinivasan; Fiona Carr; Roger Tavendale; Karen Wilson; Natalia Hernandez Pacheco; James D Chalmers; Steve Turner; Somnath Mukhopadhyay; Anke Hilse Maitland van der Zee; Esteban G Burchard; Maria Pino Yanes; Simon Young; Glenda Lassi; Adam Platt; Colin NA Palmer

    Leukotrienes play a central pathophysiological role in both pediatric and adult asthma. However, 35% to 78% of asthmatics do not respond to leukotriene inhibitors. To test the role of the LTA4H regulatory variant rs2660845 and age of asthma onset in response to montelukast in ethnically diverse populations. We identified and genotyped 3,594 asthma patients treated with montelukast (2,514 late onset

    更新日期:2020-10-06
  • The Genomic Landscape of Pediatric Rheumatology Disorders in the Middle East
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-04
    Basil Fathalla; Ali Alsarhan; Samina Afzal; Maha El Naofal; Ahmad Abou Tayoun

    Purpose: The goal of this study is to characterize the genomic landscape of pediatric rheumatological disorders in the Middle East, and to assess the clinical utility of genetic findings in this group of patients. Methods: Seventy-one pediatric patients were clinically and genetically assessed for a spectrum of rheumatology-related disease at the only dedicated tertiary childrens hospital in the United

    更新日期:2020-10-04
  • InDelible: Detection and Evaluation of Clinically-relevant Structural Variation from Exome Sequencing
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-02
    Eugene J Gardner; Alejandro Sifrim; Sarah J Lindsay; Elena Prigmore; Dianna Rajan; Petr Danecek; Giuseppe Gallone; Ruth Y Eberhardt; Hilary C Martin; Caroline F Wright; David R FitzPatrick; Helen V Firth; Matthew E Hurles

    Purpose Identifying structural variations (SVs) associated with developmental disorder (DD) patient phenotype missed by conventional approaches. Methods We have developed a novel SV discovery approach that mines split-read information, 'InDelible', and applied it to exome sequencing (ES) of 13,438 probands with severe DD recruited as part of the Deciphering Developmental Disorders (DDD) study. Results

    更新日期:2020-10-04
  • The genetic architecture of medication-use
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-02
    Palle Duun Duun Rohde; Peter Sorensen; Mette Nyegaard

    Genomics has been forecasted to revolutionise human health by improving medical treatment through a better understanding of the molecular mechanisms of human diseases. Despite great successes of the last decade's genome-wide association studies (GWAS), the results have to a limited extent been translated to genomic medicine. We propose, that one route to get closer to improved medical treatment is

    更新日期:2020-10-04
  • An integrative multi-omics approach in Sjogrens Syndrome identifies novel genetic drivers with regulatory function and disease-specificity
    medRxiv. Genet. Genom. Med. Pub Date : 2020-10-01
    Elena Carnero-Montoro; Maria Teruel; Guillermo Barturen; Manuel Martinez-Bueno; Martin Kerick; Miguel Barroso; Olivia Castellini-Perez; Elena Povedano; Francesc Catalla-Moll; Zuzanna Makowska; Anne Buttgereit; PRECISESADS Clinical Consortium; PRECISESADS Flow Cytometry Study Group; Jacques-Olivier Pers; Concepcion Maranon; Esteban Ballestar; Javier Martin; Marta Eugenia Alarcon-Riquelme

    Primary Sjogrens syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study we identified vast coordinated hypomethylation and overexpression effects, that also exhibit increased variability

    更新日期:2020-10-02
  • Genome-wide analyses in 1,987,836 participants identify 39 genetic loci associated with sleep apnoea
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-30
    Adrian I Campos; Nathan Ingold; Yunru Huang; Pik Fang Kho; Xikun Han; Jue-Sheng Ong; Luis M. Garcia-Marin; 23andMe Research Team; Matthew H. Law; Nicholas G. Martin; Xianjun Dong; Gabriel Cuellar-Partida; Stuart MacGregor; Stella Aslibekyan; Miguel E. Renteria

    Rationale: Sleep apnoea is a complex disorder characterised by periods of halted breathing during sleep. Despite its association with serious health conditions such as cardiovascular disease, the aetiology of sleep apnoea remains understudied, and previous genetic studies have failed to identify replicable genetic risk factors. Objective: To advance our understanding of factors that increase susceptibility

    更新日期:2020-10-02
  • Alzheimer's disease variant portal (ADVP): a catalog of genetic findings for Alzheimer's disease
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-30
    Pavel P Kuksa; Chia-Lun Lui; Wei Fu; Liming Qu; Yi Zhao; Zivadin Katanic; Amanda B Kuzma; Pei-Chuan Ho; Kai-Teh Tzeng; Otto Valladares; Shin-Yi Chou; Adam C Naj; Gerard D Schellenberg; Li-San Wang; Yuk Yee Leung

    Background: Alzheimer's disease (AD) genetic findings span progressively larger genome-wide association studies (GWASs) for various outcomes and populations. These genetic findings are obtained from a single GWAS, joint- or meta- analyses of multiple GWAS datasets. However, no single resource provides harmonized and searchable information on all AD genetic associations obtained from these analyses

    更新日期:2020-10-02
  • exRNA Signatures in Extracellular Vesicles and their Tumor-Lineage from Prostate Cancer
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-30
    Navneet Dogra; Mehmet Eren Ahsen; Edgar Gonzalez Kozlova; Tzu-yi Chen; kimaada allette; Reena Olsen; Dan Han; Sungcheol Kim; Stacey M. Gifford; Joshua T. Smith; Benjamin H. Wunsch; Rachel Weil; Kamala Bhatt; kamlesh K. Yadav; konstantinos vlachos; Sujit Nair; Ronald E. Gordon; Melissa Smith; Robert Sebra; Adam Margolin; Susmita Sahoo; Ashutosh Tewari; Carlos Cordon-Cardo; Bojan Losic; Gustavo A Stolovitzky

    Circulating extracellular vesicles (EVs) present in the bodily fluids of patients with cancer may provide non-invasive access to the tumor tissue. Yet, the transcriptomic lineage of tumor-derived EVs before and after tumor-resection remains poorly understood. Here, we established 60 total small RNA-sequencing profiles from 17 aggressive prostate cancer (PCa) patients tumor and adjacent normal tissue

    更新日期:2020-10-02
  • Two Color Single Molecule Sequencing on GenoCare 1600 Platform to Facilitate Clinical Applications
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-29
    Fang Chen; Bin Liu; Meirong Chen; Zefei Jiang; Zhiliang Zhou; Ping Wu; Meng Zhang; Huan Jin; Linsen Li; Liuyan Lu; Qi Wang; Huan Shang; Bing Xie; Lei Liu; Xia Lin; Weiyue Chen; Jianfeng Xu; Ruitao Sun; Guangming Wang; Jiao Zheng; Jifang Qi; Bo Yang; Dexia Chen; Lidong Zeng; Gailing Li; Yan Li; Hui Lv; Nannan Zhao; Bo Zhou; Wen Wang; Jinsen Cai; Siyu Liu; Weiwei Luo; Juan Zhang; Yanhua Zhang; Yongyi

    With the rapid development of precision medicine industry, DNA sequencing becomes increasingly important as a research and diagnosis tool. For clinical applications, medical professionals require a platform which is fast, easy to use, and presents clear information relevant to definitive diagnosis. We have developed a single molecule desktop sequencing platform, GenoCare 1600. Fast library preparation

    更新日期:2020-09-30
  • A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-29
    Alec T McIntosh; Renhuizi Wei; Jaeil Ahn; Brad E Aouizerat; Seble G Kassaye; Michael H Augenbraun; Jennifer C Price; Audrey L French; Stephen J Gange; Kathryn M Anastos; Radoslav Goldman

    HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated

    更新日期:2020-09-29
  • Systematic review and meta-analysis identifies potential host therapeutic targets in COVID-19.
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-27
    Nicholas Parkinson; Natasha Rodgers; Max Head Fourman; Bo Wang; Marie Zechner; Maaike Swets; Jonathan E Millar; Andy Law; Clark Russell; J Kenneth Baillie; Sara Clohisey

    The increasing body of literature describing the role of host factors in COVID- 19 pathogenesis demonstrates the need to combine diverse, multi-omic data to evaluate and substantiate the most robust evidence and inform development of therapies. Here we present a dynamic ranking of host genes implicated in human betacoronavirus infection (SARS-CoV-2, SARS-CoV, MERS-CoV, seasonal coronaviruses). Researchers

    更新日期:2020-09-28
  • Evidence for non-Mendelian inheritance in spastic paraplegia 7
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-27
    Mehrdad A Estiar; Eric Yu; Ikhlass Haj Salem; Jay P Ross; Kheireddin Mufti; Fulya Akcimen; Etienne Leveille; Dan Spiegelman; Jennifer A Ruskey; Farnaz Asayesh; Alain Dagher; Grace Yoon; Mark Tarnopolsky; Kym M Boycott; Nicolas Dupre; Patrick A Dion; Oksana Suchowersky; Jean-Francois Trempe; Guy A Rouleau; Ziv Gan-Or

    Hereditary spastic paraplegia is a group of rare motor neuron diseases considered to be inherited in a classical monogenic Mendelian manner. Although the typical inheritance of spastic paraplegia type 7 is autosomal recessive, several reports have suggested that SPG7 variants may also cause autosomal dominant HSP. We aimed to conduct an exome-wide genetic analysis on a large Canadian cohort of hereditary

    更新日期:2020-09-28
  • Implications of Genetic Distance to Reference and De Novo Genome Assembly for Clinical Genomics in Africans
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-27
    Daniel Shriner; Adebowale Adeyemo; Charles Rotimi

    In clinical genomics, variant calling from short-read sequencing data typically relies on a pan-genomic, universal human reference sequence. A major limitation of this approach is that the number of reads that incorrectly map or fail to map increase as the reads diverge from the reference sequence. In the context of genome sequencing of genetically diverse Africans, we investigate the advantages and

    更新日期:2020-09-28
  • Disease association with frequented regions of genotype graphs
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-27
    Samuel Hokin; Alan Cleary; Joann Mudge

    Complex diseases, with many associated genetic and environmental factors, are a challenging target for genomic risk assessment. Genome-wide association studies (GWAS) associate disease status with, and compute risk from, individual common variants, which can be problematic for diseases with many interacting or rare variants. In addition, GWAS typically employ a reference genome which is not built from

    更新日期:2020-09-28
  • Genome-wide postnatal changes in immunity following fetal inflammatory response
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-25
    Daniel Costa; Nuria Bonet; Amanda Sole; Jose Manuel Gonzalez de Aledo-Castillo; Eduard Sabido; Ferran Casals; Carlota Rovira; Alfons Nadal; Jose Luis Marin; Teresa Cobo; Robert Castelo

    The fetal inflammatory response (FIR) increases the risk of perinatal brain injury, particularly in extremely low gestational age newborns (ELGANs, < 28 weeks of gestation). One of the mechanisms contributing to such a risk is a postnatal intermittent or sustained systemic inflammation (ISSI) following FIR. The link between prenatal and postnatal systemic inflammation is supported by the presence of

    更新日期:2020-09-25
  • Genotype-phenotype correlations and novel molecular insights into the DHX30-associated neurodevelopmental disorders
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-25
    Ilaria Mannucci; Nan Cher Yeo; Hannes Huber; Jaclyn Murry; Jeff Abramson; Thorsten Althoff; Siddharth Banka; Gareth Baynam; David Bearden; Ana Beleza; Paul Benke; Siren Berland; Tatjana Bierhals; Frederic Bilan; Laurence Bindoff; Gewir Julius Braathen; Oeyvind Loevold Busk; Jirat Chenbhanich; Nghi Dang; Jonas Denecke; Luis Escobar; Caroline Estes; Julie Fleischer; Daniel Groepper; Charlotte Haaxma;

    Background We aimed to define the clinical and mutational spectrum, and to provide novel molecular insights into DHX30-associated neurodevelopmental disorder. Methods Clinical and genetic data from affected individuals were collected through family support group, GeneMatcher and our network of collaborators. Novel missense variants were investigated by in-vitro and in-vivo assays. These analyses included

    更新日期:2020-09-25
  • A multiethnic GWAS meta-analysis of 585,243 individuals identifies new risk loci associated with cataract and reveals sex-specific effects
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-24
    Helene Choquet; Ronald B. Melles; Deepti Anand; Jie Yin; Gabriel Cuellar-Partida; Wei Wang; Thomas J. Hoffmann; Saidas K. Nair; Pirro Hysi; Salil A. Lachke; Eric Jorgenson

    Cataract is the leading cause of blindness among the elderly worldwide and cataract surgery is one of the most common operations performed in the United States1-3. The etiology remains largely unclear, and to contribute to its elucidation we conducted a multiethnic genome-wide association meta-analysis of cataract, combining results from the GERA and UK Biobank cohorts, and tested for replication in

    更新日期:2020-09-24
  • Using Histopathology Images to Predict Chromosomal Instability in Breast Cancer: A Deep Learning Approach
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-24
    Zhuoran Xu; Akanksha Verma; Uska Naveed; Samuel Bakhoum; Pegah Khosravi; Olivier Elemento

    Chromosomal instability (CIN) is a hallmark of human cancer that involves mis-segregation of chromosomes during mitosis, leading to aneuploidy and genomic copy number heterogeneity. CIN is a prognostic marker in a variety of cancers, yet, gold-standard experimental assessment of chromosome mis-segregation is difficult in the routine clinical setting. As a result, CIN status is not readily testable

    更新日期:2020-09-24
  • Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-24
    Julia Goodrich; Moriel Singer-Berk; Rachel Son; Abigail Sveden; Jordan Wood; Eleina England; Joanne B. Cole; Ben Weisburd; Nick Watts; Zachary Zappala; Haichen Zhang; Kristin A. Maloney; Andy Dahl; Carlos A. Aguilar-Salinas; Gil Atzmon; Francisco Barajas-Olmos; Nir Barzilai; John Blangero; Eric Boerwinkle; Lori L. Bonnycastle; Erwin Bottinger; Donald W. Bowden; Federico Centeno- Cruz; John C. Chambers;

    Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier will develop the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from

    更新日期:2020-09-24
  • Improving reporting standards for polygenic scores in risk prediction studies
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-23
    Hannah Wand; Samuel A Lambert; Cecelia Tamburro; Michael A Iacocca; Jack W O'Sullivan; Catherine Sillari; Iftikhar J Kullo; Robb Rowley; Jacqueline S Dron; Deanna Brockman; Eric Venner; Mark I McCarthy; Antonis C Antoniou; Douglas F Easton; Robert A Hegele; Amit V Khera; Nilanjan Chatterjee; Charles Kooperberg; Karen Edwards; Katherine R Vlessis; Kim Kinnear; John N Danesh; Helen Parkinson; Erin M

    Polygenic risk scores (PRS), often aggregating the results from genome-wide association studies, can bridge the gap between the initial variant discovery efforts and disease risk estimation for clinical applications. However, there is remarkable heterogeneity in the reporting of these risk scores due to a lack of adherence to reporting standards and no accepted standards suited for the current state

    更新日期:2020-09-24
  • Genome-wide association studies reveal novel locus with sex-/therapy-specific fracture risk effects in childhood cancer survivors
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-23
    Cindy Im; Nan Li; Wonjong Moon; Qi Liu; Lindsay M Morton; Wendy M Leisenring; Rebecca M Howell; Eric J Chow; Charles A Sklar; Carmen L Wilson; Zhaoming Wang; Yadav Sapkota; Wassim Chemaitilly; Kirsten K Ness; Melissa M Hudson; Leslie L Robison; Smita Bhatia; Gregory T Armstrong; Yutaka Yasui

    Survivors of childhood cancer treated with radiation therapy (RT) and osteotoxic chemotherapies are at increased risk for fractures. However, research focusing on how genetic and clinical susceptibility factors jointly contribute to fracture risk among long-term (≥5 years) survivors of childhood cancer has been limited. To address this gap, we conducted genome-wide association studies of fracture risk

    更新日期:2020-09-23
  • Genetic Architecture of 11 Major Psychiatric Disorders at Biobehavioral, Functional Genomic, and Molecular Genetic Levels of Analysis
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-23
    Andrew D. Grotzinger; Travis T. Mallard; Wonuola A. Akingbuwa; Hill F. Ip; Mark J. Adams; Cathryn M. Lewis; Andrew M. McIntosh; Jakob Grove; Søren Dalsgaard; Klaus Peter-Lesch; Nora Strom; Sandra M. Meier; Manuel Mattheisen; Anders D. Børglum; Ole Mors; Gerome Breen; iPSYCH; Tourette Syndrome and Obsessive Compulsive Disorder Working Group of the PGC; Bipolar Disorder Working Group of the PGC; Major

    We systematically interrogate the joint genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic, and molecular genetic levels of analysis. We identify four broad factors (Neurodevelopmental, Compulsive, Psychotic, and Internalizing) that underlie genetic correlations among the disorders, and test whether these factors adequately explain their genetic correlations

    更新日期:2020-09-23
  • Molecular diagnosis of non-syndromic hearing loss patients using a stepwise approach
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-23
    Jing Wang; Jiale Xiang; Lisha Chen; Hongyu Luo; Jingjing Xu; Nana Song; Jiguang Peng; Zhiyu Peng; Xiuhua Xu; Nan Li; Chunming Cui

    Background Hearing loss is one of the most common birth disorders in humans with an estimated prevalence of 1-3 in every 1000 newborns. This study has investigated the molecular etiology of a deaf cohort using a stepwise strategy to effectively diagnose patients and the challenges faced to verify genetic heterogenicity and the variable mutation spectrums of hearing loss. Methods In order to target

    更新日期:2020-09-23
  • Craniofacial features of 3q29 deletion syndrome: application of next generation phenotyping technology.
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-23
    Bryan C Mak; Rossana Sanchez Russo; Michael J Gambello; Emily Black; Elizabeth Leslie; Melissa M Murphy; The Emory 3q29 Project; Jennifer Mulle

    Introduction: 3q29 deletion syndrome (3q29del) is a recurrent deletion syndrome associated with neuropsychiatric disorders and congenital anomalies. Dysmorphic facial features have been described but not systematically characterized. This study aims to detail the 3q29del craniofacial phenotype and use a machine learning approach to categorize individuals with 3q29del through analysis of 2D photos.

    更新日期:2020-09-23
  • Large-Scale Hypothesis Testing for Causal Mediation Effects with Applications in Genome-wide Epigenetic Studies
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-23
    Zhonghua Liu; Jincheng Shen; Richard Barfield; Joel Schwartz; Andrea Baccarelli; Xihong Lin

    In genome-wide epigenetic studies, it is of great scientific interest to assess whether the effect of an exposure on a clinical outcome is mediated through DNA methylations. However, statistical inference for causal mediation effects is challenged by the fact that one needs to test a large number of composite null hypotheses across the whole epigenome. Two popular tests, the Wald-type Sobel's test

    更新日期:2020-09-23
  • Caregiver perspectives on a diagnosis of 3q29 deletion
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-23
    Megan R. Glassford; Ryan H. Purcell; Sarah Pass; Melissa M. Murphy; Gary J. Bassell; Jennifer G. Mulle

    Objective: Genetic diagnoses are increasingly common in cases of intellectual disability and developmental delay. While ascertainment of a relatively common, well-studied variant may provide guidance related to treatments and developmental expectations, it is less clear how the diagnosis of a rare variant impacts caregivers, especially when the phenotype may include later onset manifestations such

    更新日期:2020-09-23
  • Trans-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-23
    Anubha Mahajan; Cassandra N Spracklen; Weihua Zhang; Maggie CY Ng; Lauren E Petty; Hidetoshi Kitajima; Grace Z Yu; Sina Rueger; Leo Speidel; Young Jin Kim; Momoko Horikoshi; Josep M Mercader; Daniel Taliun; Sanghoon Moon; Soo-Heon Kwak; Neil R Robertson; Nigel W Rayner; Marie Loh; Bong-Jo Kim; Joshua Chiou; Irene Miguel-Escalada; Pietro della Briotta Parolo; Kuang Lin; Fiona Bragg; Michael H Preuss;

    We assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (p<5x10-8), including 237 attaining a more stringent trans-ancestry threshold (p<5x10-9), which were delineated to 338 distinct association signals. Trans-ancestry meta-regression

    更新日期:2020-09-23
  • Multiple measures of depression to enhance validity of Major Depressive Disorder in the UK Biobank
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-22
    Kylie Patricia Glanville; Jonathan RI Coleman; David M Howard; Oliver Pain; Ken B Hanscombe; Bradley Jermy; Ryan Arathimos; Christopher Hübel; Gerome Breen; Paul F O'Reilly; Cathryn M Lewis

    Background: The UK Biobank (UKB) contains data with varying degrees of reliability and completeness for assessing depression. A third of participants completed a Mental Health Questionnaire (MHQ) containing the gold-standard Composite International Diagnostic Interview (CIDI) criteria for assessing mental health disorders. Aims: To investigate whether multiple observations of depression from sources

    更新日期:2020-09-23
  • Cancer Diagnosis, Polygenic Risk, and Longevity-Associated Variants.
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-22
    Laura Goetz; Janith Don; Andrew Schork; David Duggan; Nathan Price; Daniel Evans; Steven Cummings; Thomas Perls; Paola Sebastiani; Nicholas Schork

    Background: Polygenic risk scores (PRS) have been developed to predict individual cancer risk and their potential clinical utility is receiving a great deal of attention. However, the degree to which the predictive utility of individual cancer-specific PRS may be augmented or refined by the incorporation of other cancer PRS, non-cancer disease PRS, or the protective effects of health and longevity-associated

    更新日期:2020-09-22
  • The Causal Effects of Blood Iron and Copper on Lipid Metabolism Disease: Evidence from Phenome-wide Mendelian Randomization Study
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-22
    Jingqi Zhou; Chang Liu; Michael Francis; Yitang Sun; Moon-Suhn Ryu; Arthur Grider; Kaixiong Ye

    Background: Blood levels of iron and copper, even within their normal ranges, have been associated with a wide range of clinical outcomes. Available epidemiological evidence on blood iron and copper association with potential clinical effects, such as lipid metabolism disorder, is inconsistent and scarce. This study aims to examine and disentangle the causal clinical effects of iron and copper. Methods:

    更新日期:2020-09-22
  • A functional variant of the SIDT2 gene involved in cholesterol transport is associated with HDL-C levels and premature coronary artery disease.
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-20
    Paola Leon-Mimila; Hugo Villamil-Ramirez; Luis R. Macias-Kauffer; Leonor Jacobo-Albavera; Blanca E. Lopez-Contreras; Rosalinda Posadas-Sanchez; Carlos Posadas-Romero; Sandra Romero-Hidalgo; Sofia Moran-Ramos; Mayra Dominguez-Perez; Marisol Olivares-Arevalo; Priscilla Lopez-Montoya; Roberto Nieto-Guerra; Victor Acuna-Alonzo; Gaston Macin-Perez; Rodrigo Barquera-Lozano; Blanca E. del Rio-Navarro; Israel

    Low HDL-C is the most frequent dyslipidemia in Mexicans, but few studies have examined the underlying genetic basis. Moreover, few lipid-associated variants have been tested for coronary artery disease (CAD) in Hispanic populations. Here, we performed a GWAS for HDL-C levels in 2,183 Mexican individuals, identifying 7 loci, including three with genome-wide significance and containing the candidate

    更新日期:2020-09-20
  • Exome sequencing identifies rare coding variants in 10 genes which confer substantial risk for schizophrenia
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-18
    Tarjinder Singh; Timothy Poterba; David Curtis; Huda Akil; Mariam Al Eissa; Jack D Barchas; Nicholas Bass; Tim B Bigdeli; Gerome Breen; Evelyn J Bromet; Peter F Buckley; William E Bunney; Jonas Bybjerg-Grauholm; William F Byerley; Sinead B Chapman; Wei J. Chen; Claire Churchhouse; Nicholas Craddock; Charles Curtis; Caroline M Cusick; Lynn DeLisi; Sheila Dodge; Michael A Escamilla; Saana Eskelinen;

    By meta-analyzing the whole-exomes of 24,248 cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in ten genes as conferring substantial risk for schizophrenia (odds ratios 3 - 50, P < 2.14 x 10^-6), and 32 genes at a FDR < 5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure, and

    更新日期:2020-09-20
  • Common genetic and clinical risk factors: Association with fatal prostate cancer in the Cohort of Swedish Men
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-18
    Minh-Phuong Huynh-Le; Roshan Karunamuni; Chun Chieh Fan; Wesley K Thompson; Kenneth Muir; Artitaya Lophatananon; Karen Tye; Alicja Wolk; Niclas Håkansson; Ian G Mills; Ole A Andreassen; Anders M Dale; Tyler M Seibert; The PRACTICAL Consortium

    Background: Clinical variables--age, family history, genetics--are used for prostate cancer risk stratification. Recently, polygenic hazard scores (PHS46, PHS166) were validated as associated with age at prostate cancer diagnosis. While polygenic scores are associated with all prostate cancer (not specific for fatal cancers), PHS46 was also associated with age at prostate cancer death. We evaluated

    更新日期:2020-09-20
  • Genetic association studies of fibromuscular dysplasia identify new risk loci and shared genetic basis with more common vascular diseases
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-18
    Adrien Georges; Min-Lee Yang; Takiy-Eddine Berrandou; Mark Bakker; Ozan Dikilitas; Soto Romuald Kiando; Lijiang Ma; Benjamin A Satterfield; Sebanti Sengupta; Mengyao Yu; Jean-Francois Deleuze; Delia Dupre; Kristina L Hunker; Sergiy Kyryachenko; Lu Liu; Laurence Amar; Chad M Brumett; Dawn M Coleman; Valentina d'Escamard; Peter de Leeuw; Natalia Fendrikova-Mahlay; Daniella Kadian-Dodov; Jun Z Li; Aurelien

    Fibromuscular dysplasia (FMD) is an arteriopathy that presents clinically by hypertension and stroke, mostly in early middle-aged women. We report results from the first genome-wide association meta-analysis of FMD including 1962 FMD cases and 7100 controls. We confirmed PHACTR1 and identified three new loci (LRP1, ATP2B1, and LIMA1) associated with FMD. Transcriptome-wide association analysis in arteries

    更新日期:2020-09-20
  • Symptoms of pediatric feeding disorders among individuals with 3q29 deletion syndrome
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-18
    Addam J. Wawrzonek; T. Lindsey Burrell; William Sharp; Scott E. Gillespie; Rebecca Pollak; The Emory 3q29 Project; Melissa M Murphy; Jennifer Mulle

    Objective: To evaluate symptoms of pediatric feeding disorders in a sample of individuals with 3q29 Deletion Syndrome. Previous research has found that individuals with 3q29 deletion syndrome (3q29Del) may experience elevated feeding concerns in early childhood; however, the specificity of these feeding concerns in this pediatric population is not well understood. Methods: We compared individuals with

    更新日期:2020-09-20
  • Mixed cytomegalovirus genotypes in HIV positive mothers show compartmentalization and distinct patterns of transmission to infants.
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-18
    Juanita Pang; Jennifer A. Slyker; Sunando Roy; Josephine Bryant; Claire Atkinson; Juliana Cudini; Carey Farquhar; Paul Griffiths; James Kiarie; Sofia Morfopoulou; Alison C. Roxby; Helena Tutill; Rachel Williams; Soren Gantt; Richard A. Goldstein; Judith Breuer

    Cytomegalovirus (CMV) is the most congenital infection (cCMVi), and is particularly common among infants born to HIV-infected women. Studies of cCMVi pathogenesis are complicated by the presence of multiple infecting maternal CMV strains, especially in HIV-positive women, and the large, recombinant CMV genome. Using newly-developed tools to reconstruct CMV haplotypes, we demonstrate anatomic CMV compartmentalization

    更新日期:2020-09-20
  • Communicating polygenic and non-genetic risk for atherosclerotic cardiovascular disease - An observational follow-up study
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-18
    Elisabeth Widen; Nella Junna; Sanni Ruotsalainen; Ida Surakka; Nina Mars; Pietari Ripatti; Juulia J Partanen; Johanna Aro; Pekka Mustonen; Tiinamaija Tuomi; Aarno Palotie; Veikko Salomaa; Jaakko Kaprio; Jukka Partanen; Kristina Hotakainen; Pasi Pollanen; Samuli Ripatti

    Background. Algorithms including both traditional risk factors and polygenic risk scores (PRS) can significantly improve prediction of atherosclerotic cardiovascular disease (ASCVD). However, the clinical benefit of adding PRS to clinical risk evaluation remains unclear. Objectives. The study evaluated the attitudes of 7,342 individuals (64% women, mean age 56 yrs) upon receiving personal genome-enhanced

    更新日期:2020-09-20
  • Integrative Genomics Analysis Reveals a Novel 21q22.11 Locus Contributing to Susceptibility of COVID-19
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-18
    Yunlong Ma; Yukuan Huang; Sen Zhao; Yinghao Yao; Yaru Zhang; Jia Qu; Nan Wu; Jianzhong Su

    The systematic identification of host genetic risk factors is essential for the understanding and treatment of COVID-19. By performing a meta-analysis of two independent genome-wide association (GWAS) summary datasets (N = 680,128), a novel locus at 21q22.11 was identified to be associated with COVID-19 infection (rs9976829 in IFNAR2 and upstream of IL10RB, OR = 1.16, 95% CI = 1.09 - 1.23, P = 2.57*10-6)

    更新日期:2020-09-20
  • Genome-wide association analysis of the human thalamus identifies novel genomic loci and reveals genetic overlap with distinct cortical regions and ten brain disorders
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-18
    Torbjorn Elvsashagen; Alexey A Shadrin; Oleksandr Frei; Dennis van der Meer; Shahram Bahrami; Vinod Jangir Kumar; Olav Smeland; Lars T. Westlye; Ole Andreassen; Tobias Kaufmann

    The thalamus is a vital communication hub in the center of the brain and consists of distinct nuclei critical for consciousness and higher-order cortical functions. Structural and functional thalamic alterations are involved in the pathogenesis of common brain disorders, yet the genetic architecture of the thalamus remains largely unknown. Here, using brain scans and genotype data from 30,114 individuals

    更新日期:2020-09-20
  • GUÍA: a digital platform to facilitate result disclosure in genetic counseling
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-18
    Sabrina A. Suckiel; Jacqueline A Odgis; Katie M. Gallagher; Jessica E. Rodriguez; Dana Watnick; Gabrielle Bertier; Monisha Sebastin; Nicole Yelton; Estefany Maria; Jessenia Lopez; Michelle Ramos; Nicole Kelly; Nehama Teitelman; Faygel Beren; Tom Kaszemacher; Kojo Davis; Irma Laguerre; Lynne D. Richardson; George A. Diaz; Nathaniel M. Pearson; Stephen B. Ellis; Christian Stolte; Mimsie Robinson; Patricia

    Purpose: Use of genomic sequencing is increasing at a pace that requires technological solutions to effectively meet the needs of a growing patient population. We developed GUÍA, a web-based application, to enhance the delivery of genomic results and related clinical information to patients and families. Methods: GUÍA development occurred in 5 phases: formative research, content development, user interface

    更新日期:2020-09-20
  • Novel FARS2 mutations in patients with non-fatal early onset encephalopathy with or without epilepsy
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-17
    Giulia Barcia; Marlène Rio; Zahra Assouline; Coralie Zangarelli; Charles-Joris Roux; Pascale de Lonlay; Julie Steffann; Isabelle Desguerre; Arnold Munnich; Jean-Paul Bonnefont; Nathalie Boddaert; Agnès Rötig; Metodi D Metodiev; Benedetta Ruzzenente

    Mitochondrial translation is essential for the biogenesis of the mitochondrial oxidative phosphorylation system (OXPHOS) that synthesizes the bulk of ATP for the cell. Mutations in either mitochondrial DNA or in nuclear genes that encode mitochondrial translation factors can result in impaired OXPHOS biogenesis and mitochondrial diseases with variable clinical presentations. Mutations in the FARS2

    更新日期:2020-09-18
  • Elucidating the Joint Genetic Architecture of Mood Disorder and Schizophrenia
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-15
    Max Lam; Meiling Thompson; Baijia Li; Alexis C Edwards; Chia-Yen Chen; Tian Ge; Na Cai; Tim Bigdeli; Todd Lencz; Kenneth Kendler; Hailiang Huang

    Introduction: Recent advances in psychiatric genomics have enabled large-scale genome-wide scans that elucidated genetic architecture both in mood disorder and schizophrenia across individuals of East Asian and European descent. Investigating joint genetic architecture of these psychiatric traits enables the identification of common and diverging etiological mechanisms underlying these psychiatric

    更新日期:2020-09-16
  • Comorbidities and Susceptibility to COVID-19: A Generalized Gene Set Meta-Analysis Approach
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-15
    Micaela F. Beckman; Chika K. Igba; Farah B. Mougeot; Jean-Luc Mougeot

    Background The COVID-19 pandemic has led to over 820,000 deaths for almost 24 million confirmed cases worldwide, as of August 27th, 2020, per WHO report. Risk factors include pre-existing conditions such as cancer, cardiovascular disease, diabetes, obesity, and cancer. There are currently no effective treatments. Our objective was to complete a meta-analysis to identify comorbidity-associated single

    更新日期:2020-09-15
  • Additional SNPs improve the performance of a polygenic hazard score for prostate cancer
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-15
    Roshan Karunamuni; Minh-Phuong Huynh-Le; Chun C Fan; Wesley Thompson; Rosalind Eeles; Zsofia Kote-Jarai; Kenneth Muir; Artitaya Lophatananon; UKGPCS collaborators; Johanna Schleutker; Nora Pashayan; Jyotsna Batra; APCB BioResource; Henrik Gronberg; Eleanor Walsh; Emma Turner; Athene Lane; Richard Martin; David Neal; Jenny Donovan; Freddie Hamdy; Borge Nordestgaard; Catherine Tangen; Robert MacInnis;

    Background: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). Materials and Method: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized

    更新日期:2020-09-15
  • Greater Effect of Polygenic Risk Score for Alzheimer's Disease Among Younger Cases Who are Apolipoprotein E-ϵ4 Carriers
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-14
    Brian Fulton-Howard; Alison M Goate; Robert P Adelson; Jeremy Koppel; Marc L Gordon; Alzheimer's Disease Genetics Consortium; Nir Barzilai; Gil Atzmon; Peter Davies; Yun Freudenberg-Hua

    To evaluate how age and Apolipoprotein E-ϵ4 (APOE4) status interact with APOE4-independent polygenic risk score (PRSnon-APOE), we estimated PRSnon-APOE in superagers (age ≥ 90 years, N=346), 89- controls (age 60-89, N=2,930) and Alzheimer's Disease (AD) cases (N=1,760). Employing superagers, we see a nearly five times greater odds ratio (OR) for AD comparing the top PRSnon-APOE decile to the lowest

    更新日期:2020-09-15
  • Rapid, accurate, nucleobase detection using FnCas9
    medRxiv. Genet. Genom. Med. Pub Date : 2020-09-14
    Mohd. Azhar; Rhythm Phutela; Manoj Kumar; Asgar Hussain Ansari; Riya Rauthan; Sneha Gulati; Namrata Sharma; Dipanjali Sinha; Saumya Sharma; Sunaina Singh; Sundaram Acharya; Deepanjan Paul; Poorti Kathpalia; Meghali Aich; Paras Sehgal; Gyan Ranjan; Rahul C Bhoyar; Indian CoV2 Genomics & Genetic Epidemiology (IndiCovGEN) Consortium; Khushboo Singhal; Harsha Lad; Pradeep Kumar Patra; Govind Makharia;

    Rapid detection of pathogenic sequences or variants in DNA and RNA through a point-of-care diagnostic approach is valuable for accelerated clinical prognosis as has been witnessed during the recent COVID-19 outbreak. Traditional methods relying on qPCR or sequencing are difficult to implement in settings with limited resources necessitating the development of accurate alternative testing strategies

    更新日期:2020-09-14