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James Broach, PhD

James Broach, PhD

Distinguished Professor and Chair, Department of Biochemistry and Molecular Biology
Professor, Department of Otolaryngology - Head and Neck Surgery
Scientific Program:Next-Generation Therapies
JRB62@psu.edu
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Research Interests

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The Dr. James Broach lab has studied a variety of biological processes using the yeast Saccharomyces as a model system.  These studies have focused primarily on the interaction of cells with their environment, exploring the nature of signaling pathways that cells use to perceive their nutritional state - such as the Ras/protein kinase A pathway and the Target of Rapamycin Complex – and the transcriptional and metabolic responses of those cells to changes in nutritional state.  More recently, the lab has focused on the cell’s stress response, using single cell imaging and genome sequencing-based studies of chromatin structure and transcriptional remodeling.  These studies yielded the remarkable finding that genetically identical cells in the same environment mount quite different responses to an applied stress, allowing the population as a whole to hedge its bets regarding the best survival strategy in the face of an uncertain future.

 

More recently, the lab has expanded its interest to the application of genomic tools to issues of disease onset and treatment. The work is conducted through the Institute for Personalized Medicine, comprising a biorepository, in which biological samples from all consented patients of the Milton S. Hershey Medical Center are stored; a genomics core, in which state of the art genotyping and NextGen sequencing is applied to the biological samples; and a bioinformatics core, in which patient outcome data obtained from electronic medical records are correlated with genomic profiling and sequencing results. The lab works closely with clinicians at the Milton S. Hershey Medical Center to identify patients whose disorder or response to treatment shows a familial pattern of inheritance, as well as cohorts of patients that have phenotypically distinct disease presentations or responses to treatment.  The lab has successfully pursued studies in a variety of diseases, including various cancers, ALS, multiple sclerosis, inflammatory bowel disease, epilepsy and osteoporosis.

  • Yeasts
  • Saccharomyces cerevisiae
  • Genes
  • Proteins
  • Plasmids
  • Mutation
  • Growth
  • Genome
  • DNA
  • Chromatin
  • Nutrients
  • Neoplasms
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Recent Publications

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2023

Costa, ACT, Russo, M, Fernandes, AAR, Broach, JR & Fernandes, PMB 2023, 'Transcriptional Response of Multi-Stress-Tolerant Saccharomyces cerevisiae to Sequential Stresses', Fermentation, vol. 9, no. 2, 195. https://doi.org/10.3390/fermentation9020195

2022

NYGC ALS Consortium 2022, 'Cell environment shapes TDP-43 function with implications in neuronal and muscle disease', Communications Biology, vol. 5, no. 1, 314. https://doi.org/10.1038/s42003-022-03253-8
Hehnly, C, Ssentongo, P, Bebell, LM, Burgoine, K, Bazira, J, Fronterre, C, Kumbakumba, E, Mulondo, R, Mbabazi-Kabachelor, E, Morton, SU, Ngonzi, J, Ochora, M, Olupot-Olupot, P, Mugamba, J, Onen, J, Roberts, DJ, Sheldon, K, Sinnar, SA, Smith, J, Ssenyonga, P, Kiwanuka, J, Paulson, JN, Meier, FA, Ericson, JE, Broach, JR & Schiff, SJ 2022, 'Cytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus', International Journal of Infectious Diseases, vol. 118, pp. 24-33. https://doi.org/10.1016/j.ijid.2022.02.005
Kumar, MS, Slud, EV, Hehnly, C, Zhang, L, Broach, J, Irizarry, RA, Schiff, SJ & Paulson, JN 2022, 'Differential richness inference for 16S rRNA marker gene surveys', Genome biology, vol. 23, no. 1, 166. https://doi.org/10.1186/s13059-022-02722-x
Labarge, B, Hennessy, M, Zhang, L, Goldrich, D, Chartrand, S, Purnell, C, Wright, S, Goldenberg, D & Broach, JR 2022, 'Human Papillomavirus Integration Strictly Correlates with Global Genome Instability in Head and Neck Cancer', Molecular Cancer Research, vol. 20, no. 9, pp. 1420-1428. https://doi.org/10.1158/1541-7786.MCR-21-0831
Shi, A, Fan, F & Broach, JR 2022, 'Microbial adaptive evolution', Journal of Industrial Microbiology and Biotechnology, vol. 49, no. 2, kuab076. https://doi.org/10.1093/jimb/kuab076
Stine, JG, Schreibman, IR, Faust, AJ, Dahmus, J, Stern, B, Soriano, C, Rivas, G, Hummer, B, Kimball, SR, Geyer, NR, Chinchilli, VM, Loomba, R, Schmitz, K, Sciamanna, C, Strine, C, Wentzel, R, Marlin, S, Sica, C, Vesek, J, Eyster, E, Sinoway, L, Bentz, K, Handley, N, Hershey Fell, B, Mottilla, S, Christ, C, George, S, Novchich, T, Beyer, M, Clarke, K, Myers, T, Glading-Steinruck, M, Krok, K, Ma, T, Riley, T, Thompson, E, Tressler, H, Broach, J, Doan, T, Patrick, S, Reed, S, Hamilton, C, Slavoski, K & Tregea, D 2022, 'NASHFit: A randomized controlled trial of an exercise training program to reduce clotting risk in patients with NASH', Hepatology, vol. 76, no. 1, pp. 172-185. https://doi.org/10.1002/hep.32274
NYGC ALS Consortium 2022, 'NOS1AP is a novel molecular target and critical factor in TDP-43 pathology', Brain Communications, vol. 4, no. 5. https://doi.org/10.1093/braincomms/fcac242
Budurlean, L, Baker, M & Broach, J 2022, 'Rare MYC-N11S germline mutation indicative of inherited breast cancer in a multigeneration family', BMJ case reports, vol. 15, no. 11, e251336. https://doi.org/10.1136/bcr-2022-251336
Wasserfall, C, Dyer, AM, Speake, C, Andersen, DK, Baab, KT, Bellin, MD, Broach, JR, Campbell-Thompson, M, Chinchilli, VM, Lee, PJ, Park, WG, Pratley, RE, Saloman, JL, Sims, EK, Tang, G, Yadav, D, Yazici, C & Conwell, DL 2022, 'Standard Operating Procedures for Biospecimen Collection, Processing, and Storage: From the Type 1 Diabetes in Acute Pancreatitis Consortium', Pancreas, vol. 51, no. 6, pp. 593-597. https://doi.org/10.1097/MPA.0000000000002077
Xu, J, Song, F, Lyu, H, Kobayashi, M, Zhang, B, Zhao, Z, Hou, Y, Wang, X, Luan, Y, Jia, B, Stasiak, L, Wong, JHY, Wang, Q, Jin, Q, Jin, Q, Fu, Y, Yang, H, Hardison, RC, Dovat, S, Platanias, LC, Diao, Y, Yang, Y, Yamada, T, Viny, AD, Levine, RL, Claxton, D, Broach, JR, Zheng, H & Yue, F 2022, 'Subtype-specific 3D genome alteration in acute myeloid leukaemia', Nature, vol. 611, no. 7935, pp. 387-398. https://doi.org/10.1038/s41586-022-05365-x
NYGC ALS Consortium 2022, 'TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A', Nature, vol. 603, no. 7899, pp. 131-137. https://doi.org/10.1038/s41586-022-04436-3
Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC) 2022, 'Type 1 Diabetes in Acute Pancreatitis Consortium: From Concept to Reality', Pancreas, vol. 51, no. 6, pp. 563-567. https://doi.org/10.1097/MPA.0000000000002073
Hehnly, C, Shi, A, Ssentongo, P, Zhang, L, Isaacs, A, Morton, SU, Streck, N, Erdmann-Gilmore, P, Tolstoy, I, Reid Townsend, R, Limbrick, DD, Paulson, JN, Ericson, JE, Galperin, MY, Schiff, SJ & Broach, JR 2022, 'Type IV Pili Are a Critical Virulence Factor in Clinical Isolates of Paenibacillus thiaminolyticus', mBio, vol. 13, no. 6. https://doi.org/10.1128/mbio.02688-22
Movassagh, M, Morton, SU, Hehnly, C, Smith, J, Doan, TT, Irizarry, R, Broach, JR, Schiff, SJ, Bailey, JA & Paulson, JN 2022, 'mirTarRnaSeq: An R/Bioconductor Statistical Package for miRNA-mRNA Target Identification and Interaction Analysis', BMC genomics, vol. 23, no. 1, 439. https://doi.org/10.1186/s12864-022-08558-w

2021

Mishra, D, Bepler, T, Teague, B, Berger, B, Broach, J & Weiss, R 2021, 'An engineered protein-phosphorylation toggle network with implications for endogenous network discovery', Science, vol. 373, no. 6550, eaav0780. https://doi.org/10.1126/science.aav0780
The NeuroLINCS Consortium & NYGC ALS Consortium 2021, 'An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients', iScience, vol. 24, no. 11, 103221. https://doi.org/10.1016/j.isci.2021.103221
Johnson, JO, Chia, R, Miller, DE, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, AE, Topp, SD, Gibbs, JR, Cookson, MR, Sabir, MS, Dalgard, CL, Troakes, C, Jones, AR, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, IP, Dobson-Stone, C, Kwok, JB, Bonkowski, ES, Palvadeau, R, Tienari, PJ, Morrison, KE, Shaw, PJ, Al-Chalabi, A, Brown, RH, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, IJ, Perlman, SJ, Glass, I, Scott, AI, Shaw, CE, Basak, AN, Landers, JE, Chiò, A, Crawford, TO, Smith, BN, Traynor, BJ, Smith, BN, Fallini, C, Gkazi, AS, Topp, SD, Scotter, EL, Kenna, KP, Keagle, P, Tiloca, C, Vance, C, Troakes, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, ALMA, McKenna-Yasek, D, McLaughlin, RL, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, GP, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, Van Rheenen, W, Rademakers, R, Van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, KL, Nicholson, GA, Blair, IP, Leblond-Manry, C, Rouleau, GA, Hardiman, O, Morrison, KE, Veldink, JH, Van Den Berg, LH, Pall, H, Turner, MR, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, JD, Gellera, C, Ratti, A, Brown, RH, Silani, V, Landers, JE, Dalgard, CL, Adeleye, A, Soltis, AR, Alba, C, Viollet, C, Bacikova, D, Hupalo, DN, Sukumar, G, Pollard, HB, Wilkerson, MD, Martinez, EMG, Abramzon, Y, Ahmed, S, Arepalli, S, Baloh, RH, Bowser, R, Brady, CB, Brice, A, Broach, J, Campbell, RH, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, VE, Dunckley, TL, Eicher, JD, England, BK, Faghri, F, Feldman, E, Floeter, MK, Fratta, P, Geiger, JT, Gerhard, G, Gibbs, JR, Gibson, SB, Glass, JD, Hardy, J, Harms, MB, Heiman-Patterson, TD, Hernandez, DG, Jansson, L, Kirby, J, Kowall, NW, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, DJL, Maragakis, NJ, Mouzat, K, Murphy, NA, Myllykangas, L, Nalls, MA, Orrell, RW, Ostrow, LW, Pamphlett, R, Pickering-Brown, S, Pioro, EP, Pletnikova, O, Pliner, HA, Pulst, SM, Ravits, JM, Renton, AE, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, JD, Scholz, SW, Sendtner, M, Sidle, KC, Simmons, Z, Singleton, AB, Smith, N, Stone, DJ, Tienari, PJ, Troncoso, JC, Valori, M, Van Damme, P, Van Deerlin, VM, Van Den Bosch, L, Zinman, L, Landers, JE, Chiò, A, Traynor, BJ, Angelocola, SM, Ausiello, FP, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Calvo, A, Canale, F, Canosa, A, Cantisani, TA, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Chiò, A, Colletti, T, Conforti, FL, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, PM, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, FO, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, MG, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, MR, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M & Zucchi, E 2021, 'Association of Variants in the SPTLC1 Gene with Juvenile Amyotrophic Lateral Sclerosis', JAMA neurology, vol. 78, no. 10, pp. 1236-1248. https://doi.org/10.1001/jamaneurol.2021.2598
Costa, ACT, Hornick, J, Antunes, TFS, Santos, AMC, Fernandes, AAR, Broach, JR & Fernandes, PMB 2021, 'Complete genome sequence and analysis of a Saccharomyces cerevisiae strain used for sugarcane spirit production', Brazilian Journal of Microbiology, vol. 52, no. 3, pp. 1087-1095. https://doi.org/10.1007/s42770-021-00444-z
Ssentongo, P, Hehnly, C, Birungi, P, Roach, MA, Spady, J, Fronterre, C, Wang, M, Murray-Kolb, LE, Al-Shaar, L, Chinchilli, VM, Broach, JR, Ericson, JE & Schiff, SJ 2021, 'Congenital Cytomegalovirus Infection Burden and Epidemiologic Risk Factors in Countries with Universal Screening: A Systematic Review and Meta-analysis', JAMA network open. https://doi.org/10.1001/jamanetworkopen.2021.20736
Goldrich, DY, Labarge, B, Chartrand, S, Zhang, L, Sadowski, HB, Zhang, Y, Pham, K, Way, H, Lai, CYJ, Pang, AWC, Clifford, B, Hastie, AR, Oldakowski, M, Goldenberg, D & Broach, JR 2021, 'Identification of somatic structural variants in solid tumors by optical genome mapping', Journal of Personalized Medicine, vol. 11, no. 2, 142, pp. 1-21. https://doi.org/10.3390/jpm11020142
Isaacs, AM, Morton, SU, Movassagh, M, Zhang, Q, Hehnly, C, Zhang, L, Morales, DM, Sinnar, SA, Ericson, JE, Mbabazi-Kabachelor, E, Ssenyonga, P, Onen, J, Mulondo, R, Hornig, M, Warf, BC, Broach, JR, Townsend, RR, Limbrick, DD, Paulson, JN & Schiff, SJ 2021, 'Immune activation during Paenibacillus brain infection in African infants with frequent cytomegalovirus co-infection', iScience, vol. 24, no. 4, 102351. https://doi.org/10.1016/j.isci.2021.102351
Raca, G, Abdel-Azim, H, Yue, F, Broach, J, Payne, JL, Reeves, ME, Gowda, C, Schramm, J, Desai, D, Dovat, E, Hu, T, Berg, AS, Bhojwani, D, Payne, KJ & Dovat, S 2021, 'Increased Incidence of IKZF1 deletions and IGH-CRLF2 translocations in B-ALL of Hispanic/Latino children—a novel health disparity', Leukemia, vol. 35, no. 8, pp. 2399-2402. https://doi.org/10.1038/s41375-021-01133-4
The American Genome Center (TAGC), The FALS Sequencing Consortium, The Genomics England Research Consortium, The International ALS/FTD Genomics Consortium (iAFGC), The International FTD Genetics Consortium (IFGC), The International LBD Genomics Consortium (iLBDGC), The NYGC ALS Consortium, the University of Maryland Brain and Tissue Bank and NIH NeuroBioBank & The PROSPECT Consortium 2021, 'Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis', Neuron, vol. 109, no. 3, pp. 448-460.e4. https://doi.org/10.1016/j.neuron.2020.11.005
Movassagh, M, Bebell, LM, Burgoine, K, Hehnly, C, Zhang, L, Moran, K, Sheldon, K, Sinnar, SA, Mbabazi-Kabachelor, E, Kumbakumba, E, Bazira, J, Ochora, M, Mulondo, R, Nsubuga, BK, Weeks, AD, Gladstone, M, Olupot-Olupot, P, Ngonzi, J, Roberts, DJ, Meier, FA, Irizarry, RA, Broach, JR, Schiff, SJ & Paulson, JN 2021, 'Vaginal microbiome topic modeling of laboring Ugandan women with and without fever', npj Biofilms and Microbiomes, vol. 7, no. 1, 75. https://doi.org/10.1038/s41522-021-00244-1

2020

Zhang, J, Lee, D, Dhiman, V, Jiang, P, Xu, J, McGillivray, P, Yang, H, Liu, J, Meyerson, W, Clarke, D, Gu, M, Li, S, Lou, S, Xu, J, Lochovsky, L, Ung, M, Ma, L, Yu, S, Cao, Q, Harmanci, A, Yan, KK, Sethi, A, Gürsoy, G, Schoenberg, MR, Rozowsky, J, Warrell, J, Emani, P, Yang, YT, Galeev, T, Kong, X, Liu, S, Li, X, Krishnan, J, Feng, Y, Rivera-Mulia, JC, Adrian, J, Broach, JR, Bolt, M, Moran, J, Fitzgerald, D, Dileep, V, Liu, T, Mei, S, Sasaki, T, Trevilla-Garcia, C, Wang, S, Wang, Y, Zang, C, Wang, D, Klein, RJ, Snyder, M, Gilbert, DM, Yip, K, Cheng, C, Yue, F, Liu, XS, White, KP & Gerstein, M 2020, 'An integrative ENCODE resource for cancer genomics', Nature communications, vol. 11, no. 1, 3696. https://doi.org/10.1038/s41467-020-14743-w
Jin, SC, Dong, W, Kundishora, AJ, Panchagnula, S, Moreno-De-Luca, A, Furey, CG, Allocco, AA, Walker, RL, Nelson-Williams, C, Smith, H, Dunbar, A, Conine, S, Lu, Q, Zeng, X, Sierant, MC, Knight, JR, Sullivan, W, Duy, PQ, DeSpenza, T, Reeves, BC, Karimy, JK, Marlier, A, Castaldi, C, Tikhonova, IR, Li, B, Peña, HP, Broach, JR, Kabachelor, EM, Ssenyonga, P, Hehnly, C, Ge, L, Keren, B, Timberlake, AT, Goto, J, Mangano, FT, Johnston, JM, Butler, WE, Warf, BC, Smith, ER, Schiff, SJ, Limbrick, DD, Heuer, G, Jackson, EM, Iskandar, BJ, Mane, S, Haider, S, Guclu, B, Bayri, Y, Sahin, Y, Duncan, CC, Apuzzo, MLJ, DiLuna, ML, Hoffman, EJ, Sestan, N, Ment, LR, Alper, SL, Bilguvar, K, Geschwind, DH, Günel, M, Lifton, RP & Kahle, KT 2020, 'Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus', Nature Medicine, vol. 26, no. 11, pp. 1754-1765. https://doi.org/10.1038/s41591-020-1090-2
Russo, M, Newell, JM, Budurlean, L, Houser, KR, Sheldon, K, Kesterson, J, Phaeton, R, Hossler, C, Rosenberg, J, DeGraff, D, Shuman, L, Broach, JR & Warrick, JI 2020, 'Mutational profile of endometrial hyperplasia and risk of progression to endometrioid adenocarcinoma', Cancer, vol. 126, no. 12, pp. 2775-2783. https://doi.org/10.1002/cncr.32822
Paulson, JN, Williams, BL, Hehnly, C, Mishra, N, Sinnar, SA, Zhang, L, Ssentongo, P, Mbabazi-Kabachelor, E, Wijetunge, DSS, Von Bredow, B, Mulondo, R, Kiwanuka, J, Bajunirwe, F, Bazira, J, Bebell, LM, Burgoine, K, Couto-Rodriguez, M, Ericson, JE, Erickson, T, Ferrari, M, Gladstone, M, Guo, C, Haran, M, Hornig, M, Isaacs, AM, Kaaya, BN, Kangere, SM, Kulkarni, AV, Kumbakumba, E, Li, X, Limbrick, DD, Magombe, J, Morton, SU, Mugamba, J, Ng, J, Olupot-Olupot, P, Onen, J, Peterson, MR, Roy, F, Sheldon, K, Townsend, R, Weeks, AD, Whalen, AJ, Quackenbush, J, Ssenyonga, P, Galperin, MY, Almeida, M, Atkins, H, Warf, BC, Lipkin, WI, Broach, JR & Schiff, SJ 2020, 'Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants', Science Translational Medicine, vol. 12, no. 563, eaba0565. https://doi.org/10.1126/scitranslmed.aba0565

2019

Bann, DV, Jin, Q, Sheldon, KE, Houser, KR, Nguyen, L, Warrick, JI, Baker, MJ, Broach, JR, Gerhard, GS & Goldenberg, D 2019, 'Genetic variants implicate dual oxidase-2 in familial and sporadic nonmedullary thyroid cancer', Cancer Research, vol. 79, no. 21, pp. 5490-5499. https://doi.org/10.1158/0008-5472.CAN-19-0721
Pool, C, Walter, V, Bann, D, Goldenberg, D, Broach, J, Hennessy, M, Cottrill, E, Washburn, E, Williams, N, Crist, H, Imamura, Y & Warrick, JI 2019, 'Molecular characterization of tumors meeting diagnostic criteria for the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)', Virchows Archiv, vol. 474, no. 3, pp. 341-351. https://doi.org/10.1007/s00428-018-02512-6
The NYGC ALS Consortium 2019, 'Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia', Cell Reports, vol. 29, no. 5, pp. 1164-1177.e5. https://doi.org/10.1016/j.celrep.2019.09.066
The ITALSGEN Consortium & The International ALS Genomics Consortium 2019, 'Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis', Annals of Neurology, vol. 85, no. 4, pp. 470-481. https://doi.org/10.1002/ana.25431
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