Medicine and Health Sciences Commons^™

Integrated Omics Endotyping Of Infants With Respiratory Syncytial Virus Bronchiolitis And Risk Of Childhood Asthma., Yoshihiko Raita, Marcos Pérez-Losada, Robert J. Freishtat, Brennan Harmon, Jonathan M Mansbach, Pedro A Piedra, Zhaozhong Zhu, Carlos A Camargo, Kohei Hasegawa

Pediatrics Faculty Publications

Respiratory syncytial virus (RSV) bronchiolitis is not only the leading cause of hospitalization in U.S. infants, but also a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically-distinct endotypes. Here, we integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicentre prospective cohort study. We identified four biologically- and clinically-meaningful endotypes: A) clinical

Concluding Commentary: Children In All Cancer Prevention Policy Decisions., Cynthia F Bearer, Lynn Goldman

Environmental and Occupational Health Faculty Publications

This interesting series of articles on Opportunities for Cancer Prevention During Early Life brings many ideas for the primary prevention of cancer in childhood, or in adults due to early life events. The economic burden not only of cancer mortality but also of lifelong morbidity among cancer survivors, as shown by Guy et al,1 raises the importance of this critical public health issue. The topics of these articles were developed during online seminars with the pioneers in this area, some of whom authored the articles. They reflect the determinants of health diagrammed so eloquently in Healthy People 2020.2 …

Fto Genotype And Weight Loss: Systematic Review And Meta-Analysis Of 9563 Individual Participant Data From Eight Randomised Controlled Trials., Katherine M Livingstone, Carlos Celis-Morales, George D Papandonatos, Bahar Erar, Jose C Florez, Kathleen A Jablonski, Cristina Razquin, Amelia Marti, Yoriko Heianza, Tao Huang, Frank M Sacks, Mathilde Svendstrup, Xuemei Sui, Timothy S Church, Tiina Jääskeläinen, Jaana Lindström, Jaakko Tuomilehto, Matti Uusitupa, Tuomo Rankinen, Wim H M Saris, Torben Hansen, Oluf Pedersen, Arne Astrup, Thorkild I A Sørensen, Lu Qi, George A Bray, Miguel A Martinez-Gonzalez, J Alfredo Martinez, Paul W Franks, Jeanne M Mccaffery, Jose Lara, John C Mathers

Epidemiology Faculty Publications

OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.

DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.

DATA SOURCES: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.

ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual …

Expanding The Phenotype Associated With Naa10-Related N-Terminal Acetylation Deficiency., Chloé Saunier, Svein Isungset Støve, Bernt Popp, Bénédicte Gérard, Marina Blenski, Nicholas Ahmew, +Several Additional Authors

Pediatrics Faculty Publications

N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ …

Recessive Mutations In Polr1c Cause A Leukodystrophy By Impairing Biogenesis Of Rna Polymerase Iii, Isabelle Thiffault, Nicole I. Wolf, Diane Forget, Kether Guerrero, Adeline Vanderver, Cas Simons, Ryan J. Taft, +17 Additional Authors

Neurology Faculty Publications

A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is …

Genetic Modifiers Of Duchenne Muscular Dystrophy And Dilated Cardiomyopathy., Andrea Barp, Luca Bello, Luisa Politano, Paola Melacini, Chiara Calore, Eric P. Hoffman, +16 Additional Authors

Genomics and Precision Medicine Faculty Publications

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset.

METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction < 50% and/or end diastolic volume > 70 mL/m2 as …

Analysis Of Schizophrenia Data Using A Nonlinear Threshold Index Logistic Model., Zhenyu Jiang, Chengan Du, Assen Jablensky, Hua Liang, Zudi Lu, Yang Ma, Kok Lay Teo

GW Biostatistics Center

Genetic information, such as single nucleotide polymorphism (SNP) data, has been widely recognized as useful in prediction of disease risk. However, how to model the genetic data that is often categorical in disease class prediction is complex and challenging. In this paper, we propose a novel class of nonlinear threshold index logistic models to deal with the complex, nonlinear effects of categorical/discrete SNP covariates for Schizophrenia class prediction. A maximum likelihood methodology is suggested to estimate the unknown parameters in the models. Simulation studies demonstrate that the proposed methodology works viably well for moderate-size samples. The suggested approach is therefore …