The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Identification of Genetic Factors that Modify Clinical Onset of Huntington’s Disease
Open accessAbstract
As a Mendelian neurodegenerative disorder, the genetic risk of Huntington's disease (HD) is conferred entirely by an HTT CAG repeat expansion whose length is the primary determinant of the rate of pathogenesis leading to disease onset. To investigate the pathogenic process that precedes disease, we used genome-wide association (GWA) analysis to identify loci harboring genetic variations that alter the age at neurological onset of HD. A chromosome 15 locus displays two independent effects that accelerate or delay onset by 6.1 years and 1.4 years, respectively, whereas a chromosome 8 locus hastens onset by 1.6 years. Association at MLH1 and pathway analysis of the full GWA results support a role for DNA handling and repair mechanisms in altering the course of HD. Our findings demonstrate that HD disease modification in humans occurs in nature and offer a genetic route to identifying in-human validated therapeutic targets in this and other Mendelian disorders.
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“DNA damage repair pathways were found to be significantly enriched in Huntington’s disease GWAS analysis”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [111]
In the citing paper
“Gene‐wide association studies have further identified SNPs in DNA maintenance genes that influence the age of onset in this disease (Lee et al, 2015; Moss et al, 2017).”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Lee et al, 2015
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Cites
Statistical significance for genomewide studies
Storey, J. D., & Tibshirani, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1530509100 · Cited by 9,692 · cited 1×
“Correction for multiple testing of pathways in the Setscreen analysis was performed using the q-value method (Storey and Tibshirani, 2003).”
MACDONALD, M. (1993) · Cell · doi:10.1016/0092-8674(93)90585-e · Cited by 8,366
Self-citationFinding the missing heritability of complex diseases
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., et al. (2009) · Nature · doi:10.1038/nature08494 · Cited by 8,336 · cited 1×
“For the past decade, genome-wide association (GWA) analysis with SNPs has extended the power of human genetic studies to complex diseases by identifying a multitude of contributing risk factors, usually of modest or weak effect (Manolio et al., 2009).”
Self-citationThe Reactome pathway Knowledgebase
Fabregat, A., Sidiropoulos, K., Garapati, P., Gillespie, M., Hausmann, K., Haw, R., Jassal, B., Jupe, S., Korninger, F., McKay, S., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1351 · Cited by 5,605
KEGG for integration and interpretation of large-scale molecular data sets
Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., & Tanabe, M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr988 · Cited by 4,848
The Gene Ontology (GO) database and informatics resource
Gene Ontology Consortium (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh036 · Cited by 4,596
The Wellcome Trust Case Control Consortium, U.K.
Mossman, K. (2008) · Scientific American · doi:10.1038/scientificamerican0108-42a · Cited by 2,714
An improved Bonferroni procedure for multiple tests of significance
SIMES, R. J. (1986) · Biometrika · doi:10.1093/biomet/73.3.751 · Cited by 2,396
Unified Huntington's disease rating scale: Reliability and consistency
Kremer, H. P. H. (1996) · Movement Disorders · doi:10.1002/mds.870110204 · Cited by 2,149
Mi, H., Muruganujan, A., & Thomas, P. D. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1118 · Cited by 1,739
PID: the Pathway Interaction Database
Schaefer, C. F., Anthony, K., Krupa, S., Buchoff, J., Day, M., Hannay, T., & Buetow, K. H. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn653 · Cited by 1,603
Huntington disease: natural history, biomarkers and prospects for therapeutics
Ross, C. A., Aylward, E. H., Wild, E. J., Langbehn, D. R., Long, J. D., Warner, J. H., Scahill, R. I., Leavitt, B. R., Stout, J. C., Paulsen, J. S., et al. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.24 · Cited by 1,016
Self-citationPathway-Based Approaches for Analysis of Genomewide Association Studies
Wang, K., Li, M., & Bućan, M. (2007) · The American Journal of Human Genetics · doi:10.1086/522374 · Cited by 860 · cited 2×
“GSEA (Wang et al., 2007) ranks genes in order of a gene-wise significance measure, then tests whether pathway genes have a significantly high rank, weighting by the significance measure.”
Detection of Huntington's disease decades before diagnosis: the Predict-HD study
Paulsen, J. S., Langbehn, D. R., Stout, J. C., Aylward, E., Ross, C. A., NANCE, M. A., Guttman, M., Johnson, S., MacDonald, M. E., Beglinger, L. J., et al. (2007) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2007.128728 · Cited by 808
Self-citationThe U.S.–Venezuela Collaborative Research Project*, & Wexler, N. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308679101 · Cited by 761
A genome-wide linkage and association scan reveals novel loci for autism
The Gene Discovery Project of Johns Hopkins & the Autism Consortium, Weiss, L. A., & Arking, D. E. (2009) · Nature · doi:10.1038/nature08490 · Cited by 619
Bourdon, A., Minai, L., Serre, V., Jaïs, J., Sarzi, E., Aubert, S., Chrétien, D., de Lonlay, P., Paquis‐Flucklinger, V., Arakawa, H., et al. (2007) · Nature Genetics · doi:10.1038/ng2040 · Cited by 536 · cited 1×
“It also regulates mitochondrial DNA content (Bourdon et al., 2007) and suppresses activation of the oxidative stress pathway (Kuo et al.”
400: A Method for Combining Non-Independent, One-Sided Tests of Significance
Brown, M. B. (1975) · Biometrics · doi:10.2307/2529826 · Cited by 473
The Mouse Genome Database (MGD): mouse biology and model systems
Bult, C. J., Eppig, J. T., Kadin, J. A., Richardson, J. E., Blake, J. A., & the Mouse Genome Database Group (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm961 · Cited by 415 · cited 1×
“, 2013), (downloaded 6/4/2013), 4) Mouse Genome Informatics (MGI) (Bult et al., 2008) (http://www.”
CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion
Lee, J.-H., Ramos, E. M., Lee, J.-H., Gillis, T., Mysore, J. S., Hayden, M. R., Warby, S. C., Morrison, P., NANCE, M. A., Ross, C. A., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e318249f683 · Cited by 383
Self-citationGene Ontology Analysis of GWA Study Data Sets Provides Insights into the Biology of Bipolar Disorder
Holmans, P., Green, E. K., Pahwa, J. S., Ferreira, M. A. R., Purcell, S. M., Sklar, P., Owen, M. J., O'Donovan, M. C., & Craddock, N. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.05.011 · Cited by 378
Self-citationSwami, M., Hendricks, A. E., Gillis, T., Massood, T., Mysore, J. S., Myers, R. H., & Wheeler, V. C. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp242 · Cited by 330
Self-citationMacKay, C., Déclais, A., Lundin, C., Agostinho, A., Deans, A. J., Macartney, T., Hofmann, K., Gartner, A., West, S. C., Helleday, T., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.021 · Cited by 319 · cited 1×
“The FAN1 nuclease plays a role in repair of DNA inter-strand cross-links but not of double-strand breaks (Kratz et al., 2010; Liu et al., 2010; MacKay et al., 2010) and has recently been identified as essential for restart of paused replication forks in DNA synthesis (Chaudhury et al.”
Kratz, K., Schöpf, B., Kaden, S., Sendoel, A., Eberhard, R., Lademann, C. A., Cannavò, E., Sartori, A. A., Hengartner, M. O., & Jiricny, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.022 · Cited by 271 · cited 1×
“The FAN1 nuclease plays a role in repair of DNA inter-strand cross-links but not of double-strand breaks (Kratz et al., 2010; Liu et al., 2010; MacKay et al., 2010) and has recently been identified as essential for restart of paused replication forks in DNA synthesis (Chaudhury et al.”
FAN1 Acts with FANCI-FANCD2 to Promote DNA Interstrand Cross-Link Repair
Liu, T., Ghosal, G., Yuan, J., Chen, J., & Huang, J. (2010) · Science · doi:10.1126/science.1192656 · Cited by 255 · cited 1×
“The FAN1 nuclease plays a role in repair of DNA inter-strand cross-links but not of double-strand breaks (Kratz et al., 2010; Liu et al., 2010; MacKay et al., 2010) and has recently been identified as essential for restart of paused replication forks in DNA synthesis (Chaudhury et al.”
Pinto, R. M., Dragileva, E., Kirby, A., Lloret, A., Lopez, E., St. Claire, J., Panigrahi, G. B., Hou, C., Holloway, K., Gillis, T., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003930 · Cited by 250 · cited 3×
“coli DNA mismatch repair gene mutL), whose mouse homolog, Mlh1, was discovered in a genome-wide genetic screen to modify somatic instability of the CAG repeat and the timing of CAG length-dependent phenotypes in the striatum of genetic HD replica CAG knockin mice (Pinto et al., 2013).”
Self-citationDragileva, E., Hendricks, A. E., Teed, A. M., Gillis, T., Lopez, E., Friedberg, E. C., Kucherlapati, R., Edelmann, W., Lunetta, K. L., MacDonald, M. E., et al. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.09.014 · Cited by 247 · cited 1×
“By contrast, inactivation of some mismatch repair genes (Msh2, Msh3, Mlh1, Mlh3) eliminates somatic instability of the CAG repeat in Htt CAG knockin mice, and knock out of Mlh1, and other mismatch repair genes, also slows the pathogenic process in these precise genetic HD replicas (Dragileva et al., 2009; Pinto et al.…”
Self-citationWarner, J. P., Barron, L. H., & Brock, D. J. H. (1993) · Molecular and Cellular Probes · doi:10.1006/mcpr.1993.1034 · Cited by 235
Observing Huntington’s Disease: the European Huntington’s Disease Network’s REGISTRY
Orth, M., Handley, O., Schwenke, C., Dunnett, S. B., Craufurd, D., Ho, A. K., Wild, E. J., Tabrizi, S. J., & Landwehrmeyer, G. B. (2010) · PLoS Currents · doi:10.1371/currents.rrn1184 · Cited by 217
Self-citationMyotubularin phosphoinositide phosphatases: cellular functions and disease pathophysiology
Hnia, K., Vaccari, I., Bolino, A., & Laporte, J. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.04.004 · Cited by 160 · cited 1×
“MTMR10, although catalytically inactive, is thought, like other suchmyotubularin-related familymembers, to heterodimerize with an active phosphatase subunit to act on phosphatidylinositol phosphates (Hnia et al., 2012).”
Genetic modifiers of Huntington's disease
Gusella, J. F., MacDonald, M. E., & Lee, J. (2014) · Movement Disorders · doi:10.1002/mds.26001 · Cited by 150 · cited 1×
“throughout life due to a completely dominant gain-of-function mechanism that leads after decades to onset of clinical signs (Gusella et al., 2014).”
Self-citationAntonacci, F., Dennis, M. Y., Huddleston, J., Sudmant, P. H., Steinberg, K. M., Rosenfeld, J. A., Miroballo, M., Graves, T., Vives, L., Malig, M., et al. (2014) · Nature Genetics · doi:10.1038/ng.3120 · Cited by 142 · cited 1×
“3 is inverted without change in copy number at low but readily measurable frequency in the normal population (Antonacci et al., 2014).”
Huntington's disease: seeing the pathogenic process through a genetic lens
Gusella, J. F., & MacDonald, M. E. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.06.009 · Cited by 141 · cited 1×
“Definition of the Phenotype for Association Analysis Within a year after the identification of the HD mutation, the inverse relationship between CAG length and age at diagnostic motor onset, which lays the foundation for a genetics-driven approach to understanding HD, was recognized (Gusella and MacDonald, 2006).”
Self-citationLynch Syndrome: An Updated Review
Sehgal, R., Sheahan, K. D., O’Connell, P. R., Hanly, A. M., Martin, S., & Winter, D. C. (2014) · Genes · doi:10.3390/genes5030497 · Cited by 140 · cited 1×
“In humans, inactivation of MLH1 and other mismatch repair genes, predominantly MSH2, MSH6, and PMS2, is associated with dinucleotide repeat instability in certain cancers (Sehgal et al., 2014).”
Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY
Orth, M., & The European Huntington 's Disease Network (2010) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2010.209668 · Cited by 136
Self-citationInteraction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease
Djoussé, L., Knowlton, B., Hayden, M., Almqvist, E. W., Brinkman, R., Ross, C., Margolis, R., Rosenblatt, A., Durr, A., Dode, C., et al. (2003) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.20190 · Cited by 135 · cited 1×
“We and others have reported that the remaining variance has a large heritable component, implicating the actions of other genetic variations in modifying HD pathogenesis and suggesting that the difference between predicted and observed age of onset could be used in genetic studies to identify modifiers (Djoussé et al.…”
Self-citationA Genome Scan for Modifiers of Age at Onset in Huntington Disease: The HD MAPS Study
Li, J.-L., Hayden, M. R., Almqvist, E. W., Brinkman, R. R., Durr, A., Dodé, C., Morrison, P. J., Suchowersky, O., Ross, C. A., Margolis, R. L., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/378133 · Cited by 126 · cited 2×
“In this report, aided by visionary HD community efforts to collect phenotypes and biosamples from large numbers of subjects with this disorder (Dorsey, 2012; Li et al., 2003; Orth et al., 2010; Paulsen et al., 2008), we apply GWA not to identify risk factors for disease but to discover genome-wide significant quantita…”
Self-citationUbiquitin–proteasome system involvement in Huntington’s disease
Ortega, Z., & Lucas, J. J. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00077 · Cited by 117 · cited 1×
“Proteasome-mediated protein degradation due to tagging by E3 ubiquitin ligases like UBR5 is critical to many cellular processes and has been a focus of HD research due to the intracellular accumulation of misfolded polyglutamine fragments of mutant huntingtin (Ortega and Lucas, 2014).”
Pontarin, G., Ferraro, P., Bee, L., Reichard, P. A., & Bianchi, V. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211289109 · Cited by 117
Dorsey, E. R., & the Huntington Study Group COHORT Investigators (2012) · PLoS ONE · doi:10.1371/journal.pone.0029522 · Cited by 101
Self-citationIonita‐Laza, I., Xu, B., Makarov, V., Buxbaum, J. D., Roos, J. L., Gogos, J. A., & Karayiorgou, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1309475110 · Cited by 85 · cited 1×
“Although no genome-wide significant GWA signal has been reported in this segment for autism, schizophrenia, or other psychiatric disorders, it has been suggested that FAN1 may drive neurodevelopmental susceptibility based upon an increased frequency of rare missense variants (Ionita-Laza et al., 2014).”
D, N. A. M., & DiFiglia, M. (2014) · Movement Disorders · doi:10.1002/mds.26020 · Cited by 83 · cited 1×
“Because targets validated to impact on the disease process in humans have been lacking for traditional small-molecule approaches to drug development, a current focus for developing an effective disease-modifying therapy is the exploration of cutting-edge nucleic acid manipulation to prevent expression of mutant huntin…”
Li, J., Hayden, M. R., Warby, S. C., Dürr, A., Morrison, P. J., NANCE, M. A., Ross, C. A., Margolis, R. L., Rosenblatt, A., Squitieri, F., et al. (2006) · BMC Medical Genetics · doi:10.1186/1471-2350-7-71 · Cited by 79
Self-citationChaudhury, I., Stroik, D. R., & Sobeck, A. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00457-14 · Cited by 72 · cited 1×
“, 2010) and has recently been identified as essential for restart of paused replication forks in DNA synthesis (Chaudhury et al., 2014).”
Common SNP-Based Haplotype Analysis of the 4p16.3 Huntington Disease Gene Region
Lee, J., Gillis, T., Mysore, J. S., Ramos, E. M., Myers, R. H., Hayden, M. R., Morrison, P. J., Nance, M., Ross, C. A., Margolis, R. L., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.01.005 · Cited by 68
Self-citationGayán, J., Brocklebank, D., Andresen, J. M., Alkorta‐Aranburu, G., Cader, M. Z., Roberts, S. A., Cherny, S. S., Wexler, N. S., Cardon, L. R., & Housman, D. E. (2008) · Genetic Epidemiology · doi:10.1002/gepi.20317 · Cited by 63
At Risk for Huntington Disease
The Huntington Study Group PHAROS Investigators* (2006) · Archives of Neurology · doi:10.1001/archneur.63.7.991 · Cited by 62
Perlis, R. H., Smoller, J. W., Mysore, J. S., Sun, M., Gillis, T., Purcell, S., Rietschel, M., Nöthen, M. M., Witt, S. H., Maier, W., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09070973 · Cited by 51 · cited 1×
“The HTT CAG repeats of DNA samples were determined by a standard PCRsequencing method at the Massachusetts General Hospital (Perlis et al., 2010; Warner et al., 1993).”
Self-citationMoskvina, V., O'Dushlaine, C., Purcell, S., Craddock, N., Holmans, P., & O'Donovan, M. C. (2011) · Genetic Epidemiology · doi:10.1002/gepi.20636 · Cited by 49 · cited 2×
“Pathway Analysis The primary pathway analysis was performed using Setscreen (Moskvina et al., 2011), with secondary analyses using ALIGATOR (Holmans et al.”
Self-citationRandomized Controlled Trial of Ethyl-Eicosapentaenoic Acid in Huntington Disease
Huntington Study Group TREND-HD Investigators (2008) · Archives of Neurology · doi:10.1001/archneur.65.12.1582 · Cited by 49
Kuo, M.-L., Sy, A. J., Xue, L., Chi, M., Lee, M. T. C., Yen, T., Chiang, M.-I., Chang, L., Chu, P. G., & Yen, Y. (2012) · Scientific Reports · doi:10.1038/srep00822 · Cited by 44 · cited 1×
“, 2007) and suppresses activation of the oxidative stress pathway (Kuo et al., 2012).”
Pontarin, G., Ferraro, P., Rampazzo, C., Kollberg, G., Holme, E., Reichard, P. A., & Bianchi, V. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.202283 · Cited by 34
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Metadata
- Authors
- Lee, J.-M., Wheeler, V. C., Chao, M. J., Vonsattel, J. P. G., Pinto, R. M., Lucente, D., Abu-Elneel, K., Ramos, E. M., Mysore, J. S., Gillis, T., MacDonald, M. E., Gusella, J. F., Harold, D., Stone, T. C., Escott-Price, V., Han, J., Vedernikov, A., Holmans, P., Jones, L., Kwak, S., Mahmoudi, M., Orth, M., Landwehrmeyer, G. B., Paulsen, J. S., Dorsey, E. R., Shoulson, I., & Myers, R. H.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 162
- Issue
- 3
- Pages
- 516-526
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4524551
- OpenAlex
- W1895398290
- Cited by
- 655
- References
- 51
- Citations by year
- 2026: 50 · 2025: 58 · 2024: 74 · 2023: 45 · 2022: 72 · 2021: 64 · 2020: 64 · 2019: 58 · 2018: 71 · 2017: 52 · 2016: 38 · 2015: 7
- FWCI
- 26.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- CHDI Foundation
- National Institutes of Health
- Medical Research Council (MR/L023784/2, MR/L012936/1, MR/L010305/1)
- National Human Genome Research Institute (X01HG006074, R01HG002449)
- National Institute of Neurological Disorders and Stroke (R01NS040068, R01NS091161, U01NS082079, R01NS073947, P50NS016367)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- Huntington's disease, age of onset, genetic modifiers, MLH1, DNA repair, therapeutic target
- MeSH terms
- MutL Protein Homolog 1, Huntingtin Protein, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 8, Humans, Huntington Disease, Nerve Tissue Proteins, Nuclear Proteins, Age of Onset, Trinucleotide Repeats, Adaptor Proteins, Signal Transducing, Genome-Wide Association Study, Genes, Modifier
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