Long-range genomic regulators of THBS1 and LTBP4 modify disease severity in duchenne muscular dystrophy

Annals of Neurology
Robert B WeissUnited Dystrophinopathy Project

Abstract

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disease caused by loss-of-function dystrophin (DMD) mutations in boys, who typically suffer loss of ambulation by age 12. Previously, we reported that coding variants in latent transforming growth factor beta (TGFβ)-binding protein 4 (LTBP4) were associated with reduced TGFβ signaling and prolonged ambulation (p = 1.0 × 10-3 ) in DMD patients; this result was subsequently replicated by other groups. In this study, we evaluated whether additional DMD modifier genes are observed using whole-genome association in the original cohort. We performed a genome-wide association study (GWAS) for single-nucleotide polymorphisms (SNPs) influencing loss of ambulation (LOA) in the same cohort of 253 DMD patients used to detect the candidate association with LTBP4 coding variants. Gene expression and chromatin interaction databases were used to fine-map association signals above the threshold for genome-wide significance. Despite the small sample size, two loci associated with prolonged ambulation met genome-wide significance and were tagged by rs2725797 (chr15, p = 6.6 × 10-9 ) and rs710160 (chr19, p = 4.7 × 10-8 ). Gene expression and chromatin interaction data indicated that ...Continue Reading

References

Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D J GoodN P Bouck
Jul 10, 1998·Cell·S E CrawfordN Bouck
Mar 10, 2000·Cytokine & Growth Factor Reviews·J E Murphy-Ullrich, M Poczatek
Jan 16, 2002·American Journal of Human Genetics·Daniel J SchaidGregory A Poland
Nov 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Judith N HaslettLouis M Kunkel
Dec 19, 2003·American Journal of Human Genetics·Christopher S CarlsonDeborah A Nickerson
Nov 29, 2005·Biochemical and Biophysical Research Communications·Yong ZhouJoanne E Murphy-Ullrich
Dec 30, 2006·PLoS Genetics·Nick PattersonDavid Reich
May 20, 2009·The Journal of Clinical Investigation·Sylvia A VetroneMelissa J Spencer
Aug 4, 2009·Genome Research·David H AlexanderKenneth Lange
Nov 4, 2009·The Journal of Clinical Investigation·Ahlke HeydemannElizabeth M McNally
May 15, 2010·Journal of Neuropathology and Experimental Neurology·Noemí De LunaIsabel Illa
Jul 16, 2010·Neuromuscular Disorders : NMD·Payam SoltanzadehKevin M Flanigan
Jul 17, 2010·Bioinformatics·Randall J PruimCristen J Willer
Dec 24, 2010·Neurology·E PegoraroUNKNOWN Cooperative International Neuromuscular Research Group
Mar 28, 2012·Annals of Neurology·Jerry R MendellRobert B Weiss
May 4, 2012·Cold Spring Harbor Perspectives in Medicine·Patrick R Lawler, Jack Lawler
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Jan 24, 2013·European Journal of Human Genetics : EJHG·Stuart J MoatLouise Hartley
Feb 27, 2013·Annals of Neurology·Kevin M FlaniganUNKNOWN United Dystrophinopathy Project
Apr 24, 2013·Bioinformatics·Kenneth LangeEric M Sobel
Oct 15, 2013·Cell·Denes HniszRichard A Young
Oct 24, 2014·Science Translational Medicine·Ermelinda CecoElizabeth M McNally
Dec 6, 2014·Journal of Neurology, Neurosurgery, and Psychiatry·Janneke C van den BergenPietro Spitali
Feb 3, 2015·Annals of Neurology·Luca BelloUNKNOWN Cooperative International Neuromuscular Research Group Investigators
Nov 20, 2015·Cell·Natassia M VieiraMayana Zatz
Feb 27, 2016·PloS One·Kay-Marie LamarElizabeth M McNally
Apr 20, 2016·The Journal of Cell Biology·Joana CapoteMelissa J Spencer
Aug 23, 2016·Nature Genetics·Shane McCarthyUNKNOWN Haplotype Reference Consortium
Oct 18, 2016·American Journal of Human Genetics·Luca BelloUNKNOWN Cooperative International Neuromuscular Research Group
Dec 25, 2016·Biochimica Et Biophysica Acta. Molecular Cell Research·Mattia QuattrocelliElizabeth M McNally
Oct 13, 2017·Nature·UNKNOWN GTEx ConsortiumStephen B Montgomery
Oct 25, 2017·PLoS Genetics·Mattia QuattrocelliElizabeth M McNally
Dec 6, 2017·Human Molecular Genetics·Norifumi UraoTimothy J Koh

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Citations

Apr 2, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maaike van PuttenAnnemieke Aartsma-Rus
Jul 11, 2019·Journal of Muscle Research and Cell Motility·Dominic J Wells
Jan 4, 2020·European Journal of Human Genetics : EJHG·Pietro SpitaliAnnemieke Aartsma-Rus
Sep 8, 2020·Muscle & Nerve·Hasan DemirciHasmet Hanagasi
Sep 13, 2020·Journal of Applied Genetics·Magdalena Mroczek, Maria Gabriela Sanchez
Apr 29, 2020·Annals of Clinical and Translational Neurology·Luca BelloElena Pegoraro
Nov 6, 2020·Muscle & Nerve·Gregory HaberVenkatesh Atul Bhattaram
Feb 25, 2021·Molecular Genetics & Genomic Medicine·Russell J ButterfieldRobert B Weiss
Jul 14, 2021·Muscle & Nerve·Mathula ThangarajhUNKNOWN CINRG-DNHS Investigators
Aug 29, 2021·Pharmaceuticals·Carlos Pascual-MorenaVicente Martínez-Vizcaíno
Dec 1, 2021·Neuropathology and Applied Neurobiology·Tatyana A VetterKevin M Flanigan

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