000268518 001__ 268518 000268518 005__ 20240808164555.0 000268518 0247_ $$2doi$$a10.1093/braincomms/fcae016 000268518 0247_ $$2pmid$$apmid:38449714 000268518 0247_ $$2pmc$$apmc:PMC10917446 000268518 0247_ $$2altmetric$$aaltmetric:160693209 000268518 037__ $$aDZNE-2024-00264 000268518 041__ $$aEnglish 000268518 082__ $$a610 000268518 1001_ $$aHong, Eun Pyo$$b0 000268518 245__ $$aModification of Huntington's disease by short tandem repeats. 000268518 260__ $$a[Großbritannien]$$bGuarantors of Brain$$c2024 000268518 3367_ $$2DRIVER$$aarticle 000268518 3367_ $$2DataCite$$aOutput Types/Journal article 000268518 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1711015296_32501 000268518 3367_ $$2BibTeX$$aARTICLE 000268518 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000268518 3367_ $$00$$2EndNote$$aJournal Article 000268518 520__ $$aExpansions of glutamine-coding CAG trinucleotide repeats cause a number of neurodegenerative diseases, including Huntington's disease and several of spinocerebellar ataxias. In general, age-at-onset of the polyglutamine diseases is inversely correlated with the size of the respective inherited expanded CAG repeat. Expanded CAG repeats are also somatically unstable in certain tissues, and age-at-onset of Huntington's disease corrected for individual HTT CAG repeat length (i.e. residual age-at-onset), is modified by repeat instability-related DNA maintenance/repair genes as demonstrated by recent genome-wide association studies. Modification of one polyglutamine disease (e.g. Huntington's disease) by the repeat length of another (e.g. ATXN3, CAG expansions in which cause spinocerebellar ataxia 3) has also been hypothesized. Consequently, we determined whether age-at-onset in Huntington's disease is modified by the CAG repeats of other polyglutamine disease genes. We found that the CAG measured repeat sizes of other polyglutamine disease genes that were polymorphic in Huntington's disease participants but did not influence Huntington's disease age-at-onset. Additional analysis focusing specifically on ATXN3 in a larger sample set (n = 1388) confirmed the lack of association between Huntington's disease residual age-at-onset and ATXN3 CAG repeat length. Additionally, neither our Huntington's disease onset modifier genome-wide association studies single nucleotide polymorphism data nor imputed short tandem repeat data supported the involvement of other polyglutamine disease genes in modifying Huntington's disease. By contrast, our genome-wide association studies based on imputed short tandem repeats revealed significant modification signals for other genomic regions. Together, our short tandem repeat genome-wide association studies show that modification of Huntington's disease is associated with short tandem repeats that do not involve other polyglutamine disease-causing genes, refining the landscape of Huntington's disease modification and highlighting the importance of rigorous data analysis, especially in genetic studies testing candidate modifiers. 000268518 536__ $$0G:(DE-HGF)POF4-354$$a354 - Disease Prevention and Healthy Aging (POF4-354)$$cPOF4-354$$fPOF IV$$x0 000268518 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000268518 650_7 $$2Other$$aHuntington’s disease 000268518 650_7 $$2Other$$aHuntington’s disease 000268518 650_7 $$2Other$$aHuntington’s disease 000268518 650_7 $$2Other$$aATXN3 000268518 650_7 $$2Other$$aHuntington’s disease 000268518 650_7 $$2Other$$agenetic modification 000268518 650_7 $$2Other$$apolyglutamine disease 000268518 650_7 $$2Other$$ashort tandem repeat 000268518 7001_ $$aRamos, Eliana Marisa$$b1 000268518 7001_ $$0P:(DE-2719)2812578$$aAziz, N Ahmad$$b2$$udzne 000268518 7001_ $$aMassey, Thomas H$$b3 000268518 7001_ $$aMcAllister, Branduff$$b4 000268518 7001_ $$aLobanov, Sergey$$b5 000268518 7001_ $$aJones, Lesley$$b6 000268518 7001_ $$aHolmans, Peter$$b7 000268518 7001_ $$aKwak, Seung$$b8 000268518 7001_ $$aOrth, Michael$$b9 000268518 7001_ $$00000-0002-7663-4080$$aCiosi, Marc$$b10 000268518 7001_ $$aLomeikaite, Vilija$$b11 000268518 7001_ $$00000-0002-8298-8264$$aMonckton, Darren G$$b12 000268518 7001_ $$aLong, Jeffrey D$$b13 000268518 7001_ $$aLucente, Diane$$b14 000268518 7001_ $$aWheeler, Vanessa C$$b15 000268518 7001_ $$aGillis, Tammy$$b16 000268518 7001_ $$aMacDonald, Marcy E$$b17 000268518 7001_ $$aSequeiros, Jorge$$b18 000268518 7001_ $$00000-0003-0681-9263$$aGusella, James F$$b19 000268518 7001_ $$00000-0001-5799-0787$$aLee, Jong-Min$$b20 000268518 773__ $$0PERI:(DE-600)3020013-1$$a10.1093/braincomms/fcae016$$gVol. 6, no. 2, p. fcae016$$n2$$pfcae016$$tBrain communications$$v6$$x2632-1297$$y2024 000268518 8564_ $$uhttps://pub.dzne.de/record/268518/files/DZNE-2024-00264%20SUP.pdf 000268518 8564_ $$uhttps://pub.dzne.de/record/268518/files/DZNE-2024-00264.pdf$$yOpenAccess 000268518 8564_ $$uhttps://pub.dzne.de/record/268518/files/DZNE-2024-00264%20SUP.pdf?subformat=pdfa$$xpdfa 000268518 8564_ $$uhttps://pub.dzne.de/record/268518/files/DZNE-2024-00264.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000268518 909CO $$ooai:pub.dzne.de:268518$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire 000268518 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812578$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE 000268518 9131_ $$0G:(DE-HGF)POF4-354$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Prevention and Healthy Aging$$x0 000268518 9141_ $$y2024 000268518 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-24 000268518 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0 000268518 915__ $$0StatID:(DE-HGF)0112$$2StatID$$aWoS$$bEmerging Sources Citation Index$$d2023-08-24 000268518 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBRAIN COMMUN : 2022$$d2023-08-24 000268518 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2022-02-21T13:34:18Z 000268518 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2022-02-21T13:34:18Z 000268518 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2023-08-24 000268518 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-24 000268518 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2023-08-24 000268518 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000268518 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2022-02-21T13:34:18Z 000268518 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2023-08-24 000268518 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-24 000268518 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-08-24 000268518 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-24 000268518 9201_ $$0I:(DE-2719)5000071$$kAG Aziz$$lPopulation & Clinical Neuroepidemiology$$x0 000268518 980__ $$ajournal 000268518 980__ $$aVDB 000268518 980__ $$aUNRESTRICTED 000268518 980__ $$aI:(DE-2719)5000071 000268518 9801_ $$aFullTexts