Cited by 657Genetic Neurodegenerative DiseasesGenetic factors in colorectal cancerHereditary Neurological Disorders

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Identification of Genetic Factors that Modify Clinical Onset of Huntington’s Disease

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Lee, Jong-Min, Wheeler, Vanessa C., Chao, Michael J., Vonsattel, Jean Paul G., Pinto, Ricardo Mouro, Lucente, Diane, Abu-Elneel, Kawther, Ramos, Eliana Marisa, Mysore, Jayalakshmi Srinidhi, Gillis, Tammy, MacDonald, Marcy E., Gusella, James F., Harold, Denise, Stone, Timothy C., Escott-Price, Valentina, Han, Jun, Vedernikov, Alexey, Holmans, Peter, Jones, Lesley, Kwak, Seung, Mahmoudi, Mithra, Orth, Michael, Landwehrmeyer, G. Bernhard, Paulsen, Jane S., Dorsey, E. Ray, Shoulson, Ira, Myers, Richard H.·2015·Cell

DOI 10.1016/j.cell.2015.07.003PMC PMC4524551

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Abstract

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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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).”
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes
MACDONALD, M. (1993) · Cell · doi:10.1016/0092-8674(93)90585-e · Cited by 8,366
Self-citation
Finding 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-citation
The 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
PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees
Mi, H., Muruganujan, A., & Thomas, P. D. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1118 · Cited by 1,739

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“5,15”
Self-citation
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“132,133 At the molecular level, HD is caused by an expanded CAG trinucleotide repeat in the huntingtin ( HTT ) gene, which produces an abnormally long polyglutamine tract in the HTT protein.”
DNA extrusion size determines pathway choice during CAG repeat expansion
Bhatia, M., Phadte, A. S., Lakhina, A., Carlo, A. R. M., Barndt, S., & Pluciennik, A. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf1393 · Cited by 4
F2,6BP restores mitochondrial genome integrity in Huntington’s disease
Chakraborty, A., Mandal, S. M., Mankevich, M., Mani, R. S., Shahabi, S., Kodavati, M. M., Sreenivasmurthy, S. G., Tapryal, N., Hamilton, D. J., Krishnan, B., et al. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.111156 · Cited by 4
“Genome-wide association studies showed a strong correlation between DNA repair deficiency and the age-dependent onset of HD (2, 3).”
Identification of genetic modifiers of somatic CAG instability in Huntington's Disease by in vivo CRISPR – Cas9 genome editing
Azevedo, A., Kovalenko, M. V., Andrew, M. A., Zhang, F., Lee, J., Wheeler, V. C., & Pinto, M. R. (2017) · Porto Biomedical Journal · doi:10.1016/j.pbj.2017.07.083 · Cited by 4
Self-citation
Beyond disease susceptibility—Leveraging genome‐wide association studies for new insights into complex disease biology
Lee, J. C. (2017) · HLA · doi:10.1111/tan.13170 · Cited by 4
Self-citation
Huntingtin turnover: modulation of huntingtin degradation by cAMP-dependent protein kinase A (PKA) phosphorylation of C-HEAT domain Ser2550
Lee, Y., Kim, H., Barker, D., Vijayvargia, R., Atwal, R. S., Specht, H., Keshishian, H., Carr, S. A., Lee, R., Kwak, S., et al. (2022) · Human Molecular Genetics · doi:10.1093/hmg/ddac165 · Cited by 4
Self-citation
Intersecting impact of CAG repeat and huntingtin knockout in stem cell-derived cortical neurons
Stocksdale, J. T., Leventhal, M. J., Lam, S., Xu, Y., Wang, Y., Wang, K. Q., Thomas, R., Faghihmonzavi, Z., Raghav, Y., Smith-Geater, C., et al. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106914 · Cited by 6
Functional Analysis of Proteins Involved in Neurodegeneration Using the Model Organism Dictyostelium
Myre, M. A., Huber, R. J., & O’Day, D. H. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-804078-2.00021-0 · Cited by 4
Disease-Modification in Huntington’s Disease: Moving Away from a Single-Target Approach
Jensen, M. P., & Barker, R. A. (2019) · Journal of Huntington s Disease · doi:10.3233/jhd-180320 · Cited by 4
Tracking Expansions of Stable and Threshold Length Trinucleotide Repeat Tracts In Vivo and In Vitro Using Saccharomyces cerevisiae
Williams, G. M., Petrides, A. K., Balakrishnan, L., & Surtees, J. A. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9784-8_3 · Cited by 3
A small molecule kicks repeat expansion into reverse
Flower, M. D., & Tabrizi, S. J. (2020) · Nature Genetics · doi:10.1038/s41588-020-0577-6 · Cited by 4
Mystery of Expansion: DNA Metabolism and Unstable Repeats
Grishchenko, I. V., Purvinsh, Y. V., & Yudkin, D. V. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-41283-8_7 · Cited by 5
Measuring movement in health and disease
Rebec, G. V., Koceja, D. M., & Bunner, K. D. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.01.021 · Cited by 4
The instability of the Huntington's disease CAG repeat mutation
Wheeler, V. C., Stone, J. C., Massey, T. H., & Pinto, R. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95672-7.00003-0 · Cited by 4
Self-citation
Assessing Decline: Visualising Progression in Huntington’s Disease using a Clinical Dashboard with Enroll-HD Data
Walker, T. M., Ghosh, B. C. P., & Kipps, C. (2017) · Journal of Huntington s Disease · doi:10.3233/jhd-170234 · Cited by 4
Estimation of genetic risk function with covariates in the presence of missing genotypes
Lee, A., Marder, K. S., Alcalay, R. N., Mejia‐Santana, H., Orr‐Urtreger, A., Giladi, N., Bressman, S., & Wang, Y. (2017) · Statistics in Medicine · doi:10.1002/sim.7376 · Cited by 4
Inherited HTT CAG repeat length does not have a major impact on Huntington disease duration
Lee, J., MacDonald, M. E., & Gusella, J. F. (2022) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2022.06.002 · Cited by 4
Self-citation
Rare Variants in the OTOG Gene Are a Frequent Cause of Familial Meniere’s DiseasePreprint
Román-Naranjo, P., Gallego‐Martinez, A., Soto-Varela, A., Arán, I., Moleon, M. D. C., Espinosa-Sánchez, J. M., Amor‐Dorado, J. C., Caletrío, Á. B., Pérez-Vázquez, P., & Lopez-Escamez, J. A. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/771527 · Cited by 4
“Oligogenic and multiallelic models have been already applied in different diseases, such as Parkinson (Lubbe et al. 2016) and Huntington’s disease (Lee et al. 2015a), explaining changes in disease progression and phenotypic variability.”
BackgroundMethod
Large-scale trans-ethnic replication and discovery of genetic associations for rare diseases with self-reported medical dataPreprint
Shringarpure, S., Wang, W. T., Jiang, Y., Acevedo, A., Dhamija, D., Cameron, B., Jubb, A. A., Yue, P., Sarov‐Blat, L., Gentleman, R. C., et al. (2021) · medRxiv · doi:10.1101/2021.06.09.21258643 · Cited by 4
“We used the Human Reference Consortium (HRC) as the second imputation reference panel 80 .”
Method
Base editing strategies to convert CAG to CAA diminish the disease-causing mutation in Huntington's diseasePreprint
Choi, D. E., Shin, J. W., Zeng, S., Hong, E. P., Jang, J.-H., Loupe, J. M., Wheeler, V. C., Stutzman, H. E., Kleinstiver, B. P., & Lee, J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.28.538700 · Cited by 4
Self-citation
Multi-OMIC analysis of Huntington disease reveals a neuroprotective astrocyte statePreprint
Paryani, F., Kwon, J., Ng, C. W., Madden, N., Ofori, K., Tang, A., Lü, H., Li, J., Mahajan, A., Davidson, S. M., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.08.556867 · Cited by 4
Self-citation
Tandem MutSβ binding to long extruded DNA trinucleotide repeats underpins pathogenic expansionsPreprint
Li, J., Wang, H., & Yang, W. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.12.571350 · Cited by 5
Actionable disease insights from bedside-to-bench investigation in fibrodysplasia ossificans progressiva
Wein, M. N., & Yang, Y. (2024) · Journal of Bone and Mineral Research · doi:10.1093/jbmr/zjae044 · Cited by 4
Lowering the HTT1a transcript as an effective therapy for Huntington’s diseasePreprint
Papadopoulou, A. S., Alterman, J. F., Landles, C., Smith, E. J., Conroy, F., Phillips, J. M., Cañibano-Pico, M., Nita, I. M., Osborne, G. F., Iqbal, A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.10.658804 · Cited by 4
Disruption of protein–protein interaction hotspots in the C-terminal domain of MLH1 confers mismatch repair deficiency
Fishwick, K. M., Vieito, D. G., Greco, G., Collotta, G., Gatti, M., Kulik, A. A., Guérois, R., Corbeski, I., Phadte, A. S., Senoussi, I., et al. (2025) · NAR Cancer · doi:10.1093/narcan/zcaf055 · Cited by 3
“Genome-wide association studies implicated several MMR genes, as well as FAN1 , as modifiers of HD onset [ 18 –20 ].”
Getting to the Root of Branched Ubiquitin Chains: A Review of Current Methods and Functions
Waltho, A., & Sommer, T. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2859-1_2 · Cited by 3
Alström syndrome—wide clinical variability within the same variant: a case report and literature review
Jecan-Toader, D., Trifa, A. P., Lucian, B., Pop, T. L., & Cainap, S. S. (2024) · Frontiers in Pediatrics · doi:10.3389/fped.2024.1463903 · Cited by 3
Baseline Variables Associated with Functional Decline in 2CARE, A Randomized Clinical Trial in Huntington’s Disease
McGarry, A. J., for the Huntington Study Group 2CARE Investigators and Coordinators, McDermott, M., Kieburtz, K. D., Peng, J. L., & Cudkowicz, M. (2020) · Journal of Huntington s Disease · doi:10.3233/jhd-190391 · Cited by 3
Distribution of the HTT Gene A1 and A2 Haplotypes Worldwide: A Systematic Review
Apolinário, T. A., Rodrigues, D. C., Lemos, M. B., Paiva, C. L. A., & Agostinho, L. A. (2020) · Clinical Medicine & Research · doi:10.3121/cmr.2020.1523 · Cited by 3
Molecular Mechanisms and Clinical Features of Huntington Disease: A Fatal Neurodegenerative Disorder with Autosomal Dominant Inheritance
Datta, N. (2024) · Columbia Undergraduate Science Journal · doi:10.52214/cusj.v17i1.10288 · Cited by 3
Genetics of Huntington’s disease and related disorders: beyond triplet repeats
Burgunder, J. (2024) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2023.49 · Cited by 3
Perinatal insults and neurodevelopmental disorders may impact Huntington's disease age of diagnosis
Barkhuizen, M., Rodrigues, F. B., Anderson, D. G., Winkens, B., Wild, E. J., Kramer, B. W. W., & Gavilanes, A. W. D. (2018) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2018.05.016 · Cited by 3
Chronic Exposure to Cadmium and Antioxidants Does Not Affect the Dynamics of Expanded CAG•CTG Trinucleotide Repeats in a Mouse Cell Culture System of Unstable DNA
Gomes-Pereira, M., & Monckton, D. G. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.606331 · Cited by 3
Suppression of trinucleotide repeat expansion in spermatogenic cells in Huntington’s disease
Cho, I. K., Easley, C. A., & Chan, A. W. S. (2022) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-022-02594-x · Cited by 3
Genetic drivers of repeat expansion disorders localize to 3-D chromatin domain boundariesPreprint
Sun, J., Zhou, L., Emerson, D. J., Gilgenast, T. G., Titus, K. R., Beagan, J. A., & Phillips‐Cremins, J. E. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/191213 · Cited by 3
Dissecting the Genomics of Spontaneous Coronary Artery Dissection
Weldy, C. S., Murtha, R., & Kim, J. B. (2022) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.122.003867 · Cited by 3
Therapeutic validation of MMR-associated genetic modifiers in a human ex vivo model of Huntington’s diseasePreprint
Ferguson, R., Goold, R., Coupland, L. A., Flower, M. D., & Tabrizi, S. J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.05.570095 · Cited by 3
Selective targeting of mutant huntingtin intron-1 improves rescue provided by antisense oligonucleotidesPreprint
Bragg, R. M., Landles, C., Smith, E. J., Osborne, G. F., Cantle, J. P., Bates, G. P., & Carroll, J. B. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.29.665998 · Cited by 3
Modifier variants in metabolic pathways are associated with an increased penetrance of Leber’s Hereditary Optic Neuropathy
Arany, E. S., Olimpio, C., Paramonov, I., & Horváth, R. (2025) · European Journal of Human Genetics · doi:10.1038/s41431-025-01860-7 · Cited by 3
Natural products proposed for the management of Huntington’s disease (HD): a comprehensive review
Salman, A., Eid, A. H., Khalaf, S. S., El‐Dessouki, A. M., El‐Shiekh, R. A., & Aly, S. H. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-04444-w · Cited by 2
“The length of the HTT CAG repeat expansion, which is the main factor influencing the rate at which the disease develops leading to disease onset, is the only factor contributing to the genetic risk of HD (Lee et al. 2015).”
Gene therapy for huntington’s disease: advances, challenges, and future perspectives
Kaushal, R., Yadav, M., Kosey, S., & Dwivedi, M. (2026) · Neurogenetics · doi:10.1007/s10048-026-00887-2 · Cited by 2
“Numerous loci outside of HTT that affect the age of onset have been found by genome-wide association studies (GWAS); many of these loci map to proteins of the DNA mismatch repair (MMR) pathway, such as MSH3, MLH1, PMS1, and PMS2 [ 11, 12 ].”
ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin
Perry, C. M., & Martin, D. D. O. (2026) · Journal of Neuroscience · doi:10.1523/jneurosci.0263-25.2026 · Cited by 2
Assessing Triplet Repeat Expansions in Human SVG-A Cell Culture
Williams, G. M., & Lahue, R. S. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9784-8_10 · Cited by 2

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: Lee, Jong-Min
Wheeler, Vanessa C.
Pinto, Ricardo Mouro
Lucente, Diane
Ramos, Eliana Marisa
Gillis, Tammy
Gusella, James F.
Harold, Denise
Han, Jun
Vedernikov, Alexey
Holmans, Peter
Jones, Lesley
Kwak, Seung
Orth, Michael
Landwehrmeyer, G. Bernhard
Paulsen, Jane S.
Shoulson, Ira
Myers, Richard H.
Venue: Cell
Publisher: Elsevier BV
Published: 2015-07
Volume: 162
Issue: 3
Pages: 516-526
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2015.07.003
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 395 d)
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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Identification of Genetic Factors that Modify Clinical Onset of Huntington’s Disease

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