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4. Safety of AADC Gene Therapy for Moderately Advanced Parkinson Disease: Three-Year Outcomes From the PD-1101 Trial

Author

Christine, Chadwick W, Richardson, R Mark, Van Laar, Amber D, Thompson, Marin E, Fine, Elisabeth M, Khwaja, Omar S, Li, Chunming, Liang, Grace S, Meier, Andreas, Roberts, Eiry W, Pfau, Madeline L, Rodman, Josh R, Bankiewicz, Krystof S, and Larson, Paul S

Subjects
Orphan Drug, Parkinson's Disease, Clinical Research, Neurodegenerative, Aging, Patient Safety, Neurosciences, Brain Disorders, Rare Diseases, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Neurological, Amino Acids, Antiparkinson Agents, Carboxy-Lyases, Genetic Therapy, Humans, Parkinson Disease, Quality of Life, Treatment Outcome, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Background and objectivesTo report final, 36-month safety and clinical outcomes from the PD-1101 trial of NBIb-1817 (VY-AADC01) in participants with moderately advanced Parkinson disease (PD) and motor fluctuations.MethodsPD-1101 was a phase 1b, open-label, dose escalation trial of VY-AADC01, an experimental AAV2 gene therapy encoding the human aromatic l-amino acid decarboxylase (AADC) enzyme. VY-AADC01 was delivered via bilateral, intraoperative MRI-guided putaminal infusions to 3 cohorts (n = 5 participants per cohort): cohort 1, ≤7.5 × 1011 vector genomes (vg); cohort 2, ≤1.5 × 1012 vg; cohort 3, ≤4.7 × 1012 vg.ResultsNo serious adverse events (SAEs) attributed to VY-AADC01 were reported. All 4 non-vector-related SAEs (atrial fibrillation and pulmonary embolism in 1 participant and 2 events of small bowel obstruction in another participant) resolved. Requirements for PD medications were reduced by 21%-30% in the 2 highest dose cohorts at 36 months. Standard measures of motor function (PD diary, Unified Parkinson's Disease Rating Scale III "off"-medication and "on"-medication scores), global impressions of improvement (Clinical Global Impression of Improvement, Patient Global Impression of Improvement), and quality of life (39-item Parkinson's Disease Questionnaire) were stable or improved compared with baseline at 12, 24, and 36 months following VY-AADC01 administration across cohorts.DiscussionsVY-AADC01 and the surgical administration procedure were well-tolerated and resulted in stable or improved motor function and quality of life across cohorts, as well as reduced PD medication requirements in cohorts 2 and 3 over 3 years.Trial registration informationNCT01973543.Classification of evidenceThis study provides Class IV evidence that, in patients with moderately advanced PD and motor fluctuations, putaminal infusion of VY-AADC01 is well tolerated and may improve motor function.

Published
2022

6. Safety and efficacy of valbenazine for the treatment of chorea associated with Huntington's disease (KINECT-HD): a phase 3, randomised, double-blind, placebo-controlled trial

Author

Adams, Jamie, Beck, Christopher, Chen, Cheryl, Nance, Martha, Testa, Claudia, Huffman, Patricia, Chesire, Amy, Marshall, Frederick, Dayalu, Praveen, Stovall, Angela, Hall, Deborah, Hawkins, Jacob, Ginsburg, Letty, Moore, Henry, Mestre, Tiago, Thompson, Tanya, Connors, Natalie, Rosas, H. Diana, Daley, Allison, Kostyk, Sandra K., Mitchell, Casey, Hellman, Amy, Houston, Sheryl, Buchanan, Danielle, McDonell, Katherine, Factor, Stewart A., Sperin, Elaine, Hurt, Andrea, Wojcieszek, Joanne, Adurogbangba, Mike, Raymond, Lynn A., Corey-Bloom, Jody, Snell, Chase, Blair, Courtney, Sung, Victor, Antonioli, Sophia, Fung, Jacqueline, Laganiere, Simon, Sierra, Luis, Mallonee, William M., Suter, Greg, Bega, Danny, Brown, Zsa Zsa, Elmer, Lawrence, Vollmar, Nancy, del Castillo, Debra, Lin, Yi-Han, Andrzejewski, Kelly, Weigel, Patricia, Hawkins, Trevor, Kirby, Kendra, Retzik-Stahr, Cimmaron, Seeberger, Lauren, Dhall, Rohit, Rassmann, Anja, Luxmore, McKenzie, Scott, Burton, Bulica, Bisena, Boyd, James, Chan, Katherine, McFarland, Nikolaus, Rizer, Kyle, Conlon, Patricia, Suski, Valerie, Rodriguez-Porcel, Federico, Wilson, Sandra, Farrell, Christine, Hunter, David, Houghton, David, Seoane, Sarah, Gibbons, Clare, Rizek, Philippe, Kuprewicz, Robin, Lo, Steven, Cuturic, Miroslav, Segro, Vicki, Greenly, Kate, Revilla, Fredy, Urrea-Mendoza, Enrique, Black, Kevin J., Davis, Thomas, Stover, Natividad, Duker, Andrew, Van Gerpen, Jay, Hedera, Peter, Ondo, William, Anderson, Karen, Bradley, Stephen, Cheung, Ken, Frank, Samuel, Furr Stimming, Erin, Claassen, Daniel O, Kayson, Elise, Goldstein, Jody, Mehanna, Raja, Zhang, Hui, Liang, Grace S, and Haubenberger, Dietrich

Published
2023
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8. Serial olfactory testing for the diagnosis of prodromal Parkinson's disease in the PARS study

Author

Jennings, Danna, Marek, Ken, Seibyl, John, Siderowf, Andrew, Stern, Matthew, Russell, David, Sethi, Kapil, Frank, Samuel, Simuni, Tanya, Hauser, Robert, Ravina, Bernard, Richards, Irene, Liang, Grace, Adler, Charles, Saunders-Pullman, Rachel, Evatt, Marian L., Lai, Eugene, Subramanian, Indu, Hogarth, Penelope, Chung, Kathryn, Vaswani, Pavan A., Morley, James F., and Marek, Kenneth

Published
2022
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12. A Wearable Movement Sensor Substudy of KINECT®-HD, a Phase 3 Trial of Valbenazine for the Treatment of Chorea Associated with Huntington’s Disease (P8-3.010)

Author

Adams, Jamie, primary, Stimming, Erin Furr, additional, Claassen, Daniel, additional, Kayson, Elise, additional, Goldstein, Jody, additional, Hinton, Sean, additional, Klepitskaya, Olga, additional, Zhang, Hui, additional, Liang, Grace, additional, Lin, Kelly, additional, Mitchell, Sean, additional, and Haubenberger, Dietrich, additional

Published
2024
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13. Factors associated with falling in early, treated Parkinson's disease: The NET-PD LS1 cohort.

Author

Chou, Kelvin L, Elm, Jordan J, Wielinski, Catherine L, Simon, David K, Aminoff, Michael J, Christine, Chadwick W, Liang, Grace S, Hauser, Robert A, Sudarsky, Lewis, Umeh, Chizoba C, Voss, Tiffini, Juncos, Jorge, Fang, John Y, Boyd, James T, Bodis-Wollner, Ivan, Mari, Zoltan, Morgan, John C, Wills, Anne-Marie, Lee, Stephen L, Parashos, Sotirios A, and NINDS NET-PD Investigators

Subjects
NINDS NET-PD Investigators, Humans, Parkinson Disease, Disease Progression, Dopamine Agents, Activities of Daily Living, Severity of Illness Index, Logistic Models, Risk Factors, Cohort Studies, Accidental Falls, Time Factors, Aged, Middle Aged, Female, Male, Datasets as Topic, Falls, NET-PD, Parkinson's disease, Neurosciences, Rehabilitation, Patient Safety, Clinical Research, Prevention, Parkinson's Disease, Neurodegenerative, Aging, Brain Disorders, Neurological, Clinical Sciences, Psychology
Abstract

BackgroundRecognizing the factors associated with falling in Parkinson's disease (PD) would improve identification of at-risk individuals.ObjectiveTo examine frequency of falling and baseline characteristics associated with falling in PD using the National Institute of Neurological Disorders and Stroke (NINDS) Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1) dataset.MethodsThe LS-1 database included 1741 early treated PD subjects (median 4year follow-up). Baseline characteristics were tested for a univariate association with post-baseline falling during the trial. Significant variables were included in a multivariable logistic regression model. A separate analysis using a negative binomial model investigated baseline factors on fall rate.Results728 subjects (42%) fell during the trial, including at baseline. A baseline history of falls was the factor most associated with post-baseline falling. Men had lower odds of post-baseline falling compared to women, but for men, the probability of a post-baseline fall increased with age such that after age 70, men and women had similar odds of falling. Other baseline factors associated with a post-baseline fall and increased fall rate included the Unified PD Rating Scale (UPDRS) Activities of Daily Living (ADL) score, total functional capacity (TFC), baseline ambulatory capacity score and dopamine agonist monotherapy.ConclusionFalls are common in early treated PD. The biggest risk factor for falls in PD remains a history of falling. Measures of functional ability (UPDRS ADL, TFC) and ambulatory capacity are novel clinical risk factors needing further study. A significant age by sex interaction may help to explain why age has been an inconsistent risk factor for falls in PD.

Published
2017

16. Human Coronary Plaque T Cells Are Clonal and Cross-React to Virus and Self

Author

Chowdhury, Roshni Roy, D’Addabbo, Jessica, Huang, Xianxi, Veizades, Stefan, Sasagawa, Koki, Louis, David M., Cheng, Paul, Sokol, Jan, Jensen, Annie, Tso, Alexandria, Shankar, Vishnu, Wendel, Ben Shogo, Bakerman, Isaac, Liang, Grace, Koyano, Tiffany, Fong, Robyn, Nau, Allison N., Ahmad, Herra, Gopakumar, Jayakrishnan, Wirka, Robert, Lee, Andrew S., Boyd, Jack, Woo, Y. Joseph, Quertermous, Thomas, Gulati, Gunsagar Singh, Jaiswal, Siddhartha, Chien, Yueh-Hsiu, Chan, Charles Kwok Fai, Davis, Mark M., and Nguyen, Patricia K.

Published
2022
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17. Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial.

Author

Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators, Kieburtz, Karl, Tilley, Barbara C, Elm, Jordan J, Babcock, Debra, Hauser, Robert, Ross, G Webster, Augustine, Alicia H, Augustine, Erika U, Aminoff, Michael J, Bodis-Wollner, Ivan G, Boyd, James, Cambi, Franca, Chou, Kelvin, Christine, Chadwick W, Cines, Michelle, Dahodwala, Nabila, Derwent, Lorelei, Dewey, Richard B, Hawthorne, Katherine, Houghton, David J, Kamp, Cornelia, Leehey, Maureen, Lew, Mark F, Liang, Grace S Lin, Luo, Sheng T, Mari, Zoltan, Morgan, John C, Parashos, Sotirios, Pérez, Adriana, Petrovitch, Helen, Rajan, Suja, Reichwein, Sue, Roth, Jessie Tatsuno, Schneider, Jay S, Shannon, Kathleen M, Simon, David K, Simuni, Tanya, Singer, Carlos, Sudarsky, Lewis, Tanner, Caroline M, Umeh, Chizoba C, Williams, Karen, and Wills, Anne-Marie

Subjects
Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators, Humans, Parkinson Disease, Disease Progression, Creatine, Antiparkinson Agents, Treatment Outcome, Drug Therapy, Combination, Follow-Up Studies, Double-Blind Method, Aged, Middle Aged, Female, Male, Medication Adherence, Brain Disorders, Parkinson's Disease, Neurosciences, Neurodegenerative, Aging, Clinical Research, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Neurological, Medical and Health Sciences, General & Internal Medicine
Abstract

ImportanceThere are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies.ObjectiveTo determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease.Design, setting, and patientsThe Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013.InterventionsParticipants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years).Main outcomes and measuresThe primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes.ResultsThe trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P

Published
2015

18. Safety and efficacy of valbenazine for the treatment of chorea associated with Huntington's disease (KINECT-HD): a phase 3, randomised, double-blind, placebo-controlled trial

Author

Stimming, Erin Furr, primary, Claassen, Daniel O, additional, Kayson, Elise, additional, Goldstein, Jody, additional, Mehanna, Raja, additional, Zhang, Hui, additional, Liang, Grace S, additional, Haubenberger, Dietrich, additional, Adams, Jamie, additional, Beck, Christopher, additional, Chen, Cheryl, additional, Nance, Martha, additional, Testa, Claudia, additional, Huffman, Patricia, additional, Chesire, Amy, additional, Marshall, Frederick, additional, Dayalu, Praveen, additional, Stovall, Angela, additional, Hall, Deborah, additional, Hawkins, Jacob, additional, Ginsburg, Letty, additional, Moore, Henry, additional, Mestre, Tiago, additional, Thompson, Tanya, additional, Connors, Natalie, additional, Rosas, H. Diana, additional, Daley, Allison, additional, Kostyk, Sandra K., additional, Mitchell, Casey, additional, Hellman, Amy, additional, Houston, Sheryl, additional, Buchanan, Danielle, additional, McDonell, Katherine, additional, Factor, Stewart A., additional, Sperin, Elaine, additional, Hurt, Andrea, additional, Wojcieszek, Joanne, additional, Adurogbangba, Mike, additional, Raymond, Lynn A., additional, Corey-Bloom, Jody, additional, Snell, Chase, additional, Blair, Courtney, additional, Sung, Victor, additional, Antonioli, Sophia, additional, Fung, Jacqueline, additional, Laganiere, Simon, additional, Sierra, Luis, additional, Mallonee, William M., additional, Suter, Greg, additional, Bega, Danny, additional, Brown, Zsa Zsa, additional, Elmer, Lawrence, additional, Vollmar, Nancy, additional, del Castillo, Debra, additional, Lin, Yi-Han, additional, Andrzejewski, Kelly, additional, Weigel, Patricia, additional, Hawkins, Trevor, additional, Kirby, Kendra, additional, Retzik-Stahr, Cimmaron, additional, Seeberger, Lauren, additional, Dhall, Rohit, additional, Rassmann, Anja, additional, Luxmore, McKenzie, additional, Scott, Burton, additional, Boyd, James, additional, Chan, Katherine, additional, McFarland, Nikolaus, additional, Rizer, Kyle, additional, Conlon, Patricia, additional, Suski, Valerie, additional, Rodriguez-Porcel, Federico, additional, Wilson, Sandra, additional, Farrell, Christine, additional, Hunter, David, additional, Houghton, David, additional, Seoane, Sarah, additional, Gibbons, Clare, additional, Rizek, Philippe, additional, Kuprewicz, Robin, additional, Lo, Steven, additional, Cuturic, Miroslav, additional, Segro, Vicki, additional, Greenly, Kate, additional, Revilla, Fredy, additional, Urrea-Mendoza, Enrique, additional, Black, Kevin J., additional, Davis, Thomas, additional, Stover, Natividad, additional, Duker, Andrew, additional, Van Gerpen, Jay, additional, Hedera, Peter, additional, Ondo, William, additional, Anderson, Karen, additional, Bradley, Stephen, additional, Cheung, Ken, additional, and Frank, Samuel, additional

Published
2023
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20. Effects of intranasal dantrolene nanoparticles on brain concentration and behavior in PS19 tau transgenic mice

Author

Vera, Robert, primary, Hong, Nicholas, additional, Jiang, Bailin, additional, Liang, Grace, additional, Eckenhoff, Maryellen F, additional, Kincaid, Halle J, additional, Browne, Veron, additional, Chellaraj, Vinolia, additional, Gisewhite, Douglas, additional, Greenberg, Michael, additional, Ranjan, Sudhir, additional, Zhu, Gaozhong, additional, and Wei, Huafeng, additional

Published
2023
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26. Serial olfactory testing for the diagnosis of prodromal Parkinson's disease in the PARS study

Author

Vaswani, Pavan A., primary, Morley, James F., additional, Jennings, Danna, additional, Siderowf, Andrew, additional, Marek, Kenneth, additional, Marek, Ken, additional, Seibyl, John, additional, Stern, Matthew, additional, Russell, David, additional, Sethi, Kapil, additional, Frank, Samuel, additional, Simuni, Tanya, additional, Hauser, Robert, additional, Ravina, Bernard, additional, Richards, Irene, additional, Liang, Grace, additional, Adler, Charles, additional, Saunders-Pullman, Rachel, additional, Evatt, Marian L., additional, Lai, Eugene, additional, Subramanian, Indu, additional, Hogarth, Penelope, additional, and Chung, Kathryn, additional

Published
2022
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28. Passive soil depressurization in Canadian homes for radon control

Author

Yunyi (Ethan) Li, Justin Berquist, Gang Nong, Janet Gaskin, Mark Vuotari, Jeff Whyte, and Liang (Grace) Zhou

Subjects
Environmental Engineering, passive soil depressurization, Geography, Planning and Development, Airflow, 0211 other engineering and technologies, chemistry.chemical_element, Radon, 02 engineering and technology, Stack effect, 010501 environmental sciences, 01 natural sciences, law.invention, mitigation, Cabin pressurization, law, Heat recovery ventilation, 021108 energy, 0105 earth and related environmental sciences, Civil and Structural Engineering, Hydrology, cold climate, radon, Building and Construction, chemistry, Ventilation (architecture), Environmental science, Ground floor, Floor slab
Abstract

Health Canada's cross-Canada residential radon survey from 2012 demonstrated roughly 7% of Canadian homes contain radon levels above the national guideline of 200 Bq/m3. British Columbia (BC) is the first province in Canada to mandate a full stack passive soil depressurization (PSD) system installed within homes in radon prone areas. All other provinces within Canada require a sealed and capped rough-in pipe. In this study, PSD systems were installed in fifteen new construction homes and retrofitted in six existing homes across three provinces in Canada. This study demonstrated the potential of well-designed PSD systems to reduce radon exposure in Canadian homes, reducing indoor radon concentration below 200 Bq/m3 in all 21 homes during multiple 30-day periods. During the winter, the PSD system was less effective in several new construction homes, whereas it appeared to operate more consistently in retrofitted existing homes. Further investigation revealed homes with a heat recovery ventilator (HRV), a ground floor bathroom, or no stack insulation were susceptible to degradation in the PSD system performance from the shoulder to winter season. Such performance degradation might be attributed to 1) HRV defrost mode causing a reduction in the ventilation air supply, 2) unsealed ground floor cut outs for the bathroom increasing the building stack effect and inducing more radon ingress through the floor slab during the winter, and 3) stacks without insulation causing frost and restricting the airflow within the stack.

Published
2022

30. RADON INFILTRATION BUILDING ENVELOPE TEST SYSTEM: EVALUATION OF BARRIER MATERIALS

Author

Yunyi Ethan Li, Jeff Whyte, Gang Nong, Janet Gaskin, Gnanamurugan Ganapathy, and Liang Grace Zhou

Subjects
Canada, Radiation, Test facility, Radiological and Ultrasound Technology, Petroleum engineering, Construction Materials, Public Health, Environmental and Occupational Health, chemistry.chemical_element, System evaluation, Radon, General Medicine, Infiltration (HVAC), respiratory tract diseases, Radon diffusion, chemistry, Air Pollutants, Radioactive, Building code, Air Pollution, Indoor, Housing, Environmental science, Radiology, Nuclear Medicine and imaging, Air barrier, Building envelope
Abstract

The performance of radon barrier materials currently available for housing foundations was evaluated using a unique radon infiltration building envelope test system that was designed to test radon prevention and mitigation systems using real world construction techniques. The reduction in radon concentration measured across the air barrier in the foundations has been used to evaluate five representative barrier materials installed in the radon infiltration building envelope test facility. The reduction in radon concentration in the mock house varied from 68% for 6 mil polyethylene to 98% for the spray polyurethane foam. The five representative barrier materials were selected after determining the radon diffusion coefficient and the corresponding radon resistance from samples of 14 barrier materials in a radon diffusion testing chamber. The Canadian experience evaluating whether radon barrier materials would satisfy building code requirements was described.

Published
2021

35. A Qualitative Study of Undergraduate Women in Engineering Project Teams.

Author

Liang, Grace J., Evans, Rick, Asadollahipajouh, Mojdeh, Kulesza, Stacey E., and Evans, Anna Glushko

Abstract

One intervention thought to foster women's interest in engineering is introducing girls to STEM or engineering activities. The argument for this is that an increase in interest early in their lives will lead to more women pursuing a career in engineering. The focus of our research is women who are thriving as undergraduate student leaders in engineering project teams. We employ a multi-case study method that involves a sequence of semi-structured interviews. This paper speaks to the findings derived from the life history interview where participants describe their early lives and pre-college education. Our inductive thematic analysis of the data indicates that: (1) The women's early familial influences allowed non-gender defined ways of being, doing, and aspiring for trying new things. (2) This re/definition of gender in relation to self is reinforced by their success in school and through their accomplishments in other extracurricular activities. Those activities were not confined or even heavily weighted toward STEM. (3) Not all of the women assumed leadership roles throughout their K-12 schooling. Nevertheless, what is common is that through academic and extracurricular engagements they developed confidence, a "can-do" attitude, and a rejection of viewing failures as defining indicators of their ability or potential. Their self-awareness, their confidence, and their persistence in the face of failure are critical because they later function as counter-narratives in the women's encounters with sexism and other forms of marginalization when in engineering and their project teams. Finally, there is some evidence to suggest that encouraging young girls to involve themselves in STEM and/or engineering may be counterproductive. By unintentionally "pushing" these young girls into engineering, rather than "allowing them to choose for themselves," we may be encouraging the adoption of masculinist gendered roles associated with engineering. [ABSTRACT FROM AUTHOR]

Published
2023

36. Development of a Bayesian inference model for assessing ventilation condition based on CO

Author

Danlin, Hou, Liangzhu Leon, Wang, Ali, Katal, Shujie, Yan, Liang Grace, Zhou, Vicky, Wang, Mark, Vuotari, Ethan, Li, and Zihan, Xie

Abstract

Outdoor fresh air ventilation plays a significant role in reducing airborne transmission of diseases in indoor spaces. School classrooms are considerably challenged during the COVID-19 pandemic because of the increasing need for in-person education, untimely and incompleted vaccinations, high occupancy density, and uncertain ventilation conditions. Many schools started to use CO

Published
2022

37. Safety of AADC Gene Therapy for Moderately Advanced Parkinson Disease: Three-Year Outcomes From the PD-1101 Trial

Author

Richardson, R, Van Laar, Amber, Thompson, Marin, Fine, Elisabeth, Khwaja, Omar, Li, Chunming, Liang, Grace, Meier, Andreas, Roberts, Eiry, Pfau, Madeline, Rodman, Josh, Bankiewicz, Krystof, Larson, Paul, and Christine, Chadwick

Abstract

BACKGROUND AND OBJECTIVES: To report final, 36-month safety and clinical outcomes from the PD-1101 trial of NBIb-1817 (VY-AADC01) in participants with moderately advanced Parkinson disease (PD) and motor fluctuations. METHODS: PD-1101 was a phase 1b, open-label, dose escalation trial of VY-AADC01, an experimental AAV2 gene therapy encoding the human aromatic l-amino acid decarboxylase (AADC) enzyme. VY-AADC01 was delivered via bilateral, intraoperative MRI-guided putaminal infusions to 3 cohorts (n = 5 participants per cohort): cohort 1, ≤7.5 × 1011 vector genomes (vg); cohort 2, ≤1.5 × 1012 vg; cohort 3, ≤4.7 × 1012 vg. RESULTS: No serious adverse events (SAEs) attributed to VY-AADC01 were reported. All 4 non-vector-related SAEs (atrial fibrillation and pulmonary embolism in 1 participant and 2 events of small bowel obstruction in another participant) resolved. Requirements for PD medications were reduced by 21%-30% in the 2 highest dose cohorts at 36 months. Standard measures of motor function (PD diary, Unified Parkinsons Disease Rating Scale III off-medication and on-medication scores), global impressions of improvement (Clinical Global Impression of Improvement, Patient Global Impression of Improvement), and quality of life (39-item Parkinsons Disease Questionnaire) were stable or improved compared with baseline at 12, 24, and 36 months following VY-AADC01 administration across cohorts. DISCUSSIONS: VY-AADC01 and the surgical administration procedure were well-tolerated and resulted in stable or improved motor function and quality of life across cohorts, as well as reduced PD medication requirements in cohorts 2 and 3 over 3 years. TRIAL REGISTRATION INFORMATION: NCT01973543. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, in patients with moderately advanced PD and motor fluctuations, putaminal infusion of VY-AADC01 is well tolerated and may improve motor function.

Published
2022

38. Regional cost effectiveness analyses for increasing radon protection strategies in housing in Canada

Author

Janet Gaskin, Liang Grace Zhou, Doug Coyle, and Jeff Whyte

Subjects
Marginal cost, Lung Neoplasms, Cost effectiveness, Health, Toxicology and Mutagenesis, Cost-Benefit Analysis, Psychological intervention, chemistry.chemical_element, Radon, lung cancer morbidity, Radiation Monitoring, Environmental health, Health care, Environmental Chemistry, Medicine, Humans, Waste Management and Disposal, Health policy, Monte Carlo simulation, residential radon, British Columbia, business.industry, cost-effectiveness analysis, building code, health policy, General Medicine, Cost-effectiveness analysis, Investment (macroeconomics), Pollution, respiratory tract diseases, chemistry, Air Pollution, Indoor, Housing, business
Abstract

The incremental cost effectiveness ratios for implementing a recent recommendation to install a more radon resistant foundation barrier were modelled for new and existing housing in 2016, for each province and territory in Canada. Cost-utility analyses were conducted, in which the health benefit of an intervention was quantified in quality-adjusted life years, to help guide policymakers considering increasing investment in radon reduction in housing to reduce the associated lung cancer burden shouldered by the health care system. Lung cancer morbidity was modelled using a lifetable analysis that incorporated lung cancer incidence and survival time for localized, regional, and distant stages of diagnoses for both non-small cell and small cell lung cancer. The model accounted for surgical or advanced lung cancer treatment costs avoided, and average health care costs incurred for radon-attributable lung cancer cases prevented by the intervention. The incremental implementation of radon interventions in the housing stock was modelled over a lifetime horizon, and a discount rate of 1.5% was adopted. This radon intervention in new housing was cost effective in all but one region, ranging from $18,075/QALY (15,704; 20,178) for the Yukon to $58,454/QALY (52,045; 65,795) for British Columbia. A sequential analysis was conducted to compare intervention in existing housing for mitigation thresholds of 200 and 100 Bq/m3. This intervention in existing housing was cost effective at a mitigation threshold of 200 Bq/m3 in regions with higher radon levels, ranging from $33,247/QALY (27,699; 39,377) for the Yukon to $61,960/QALY (46,932; 113,737) for Newfoundland, and more cost effective at a threshold of 200 than 100 Bq/m3. More lung cancer deaths can be prevented by intervention in new housing than in existing housing; it was estimated that the proposed intervention in new housing would prevent a mean of 446 (416; 477) lung cancer cases annually. The cost effectiveness of increased radon resistance in foundation barriers in housing varied widely, and would support adopting this intervention in new housing across Canada and in existing housing in higher radon regions. This study provides further evidence that the most cost effective way of responding to the geographically variable radon burden is by implementing specific regional radon reduction policies.

Published
2021

40. Effect of Creatine Monohydrate on Clinical Progression in Patients With Parkinson Disease: A Randomized Clinical Trial

Author

Kieburtz, Karl, Tilley, Barbara C., Elm, Jordan J., Babcock, Debra, Hauser, Robert, Ross, G. Webster, Augustine, Alicia H., Augustine, Erika U., Aminoff, Michael J., Bodis-Wollner, Ivan G., Boyd, James, Cambi, Franca, Chou, Kelvin, Christine, Chadwick W., Cines, Michelle, Dahodwala, Nabila, Derwent, Lorelei, Dewey, Richard B., Jr, Hawthorne, Katherine, Houghton, David J., Kamp, Cornelia, Leehey, Maureen, Lew, Mark F., Liang, Grace S. Lin, Luo, Sheng T., Mari, Zoltan, Morgan, John C., Parashos, Sotirios, Pérez, Adriana, Petrovitch, Helen, Rajan, Suja, Reichwein, Sue, Roth, Jessie Tatsuno, Schneider, Jay S., Shannon, Kathleen M., Simon, David K., Simuni, Tanya, Singer, Carlos, Sudarsky, Lewis, Tanner, Caroline M., Umeh, Chizoba C., Williams, Karen, and Wills, Anne-Marie

Published
2015
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41. Modest Gains After an 8-Week Exercise Program Correlate With Reductions in Non-traditional Markers of Cardiovascular Risk

Author

Liang, Grace, primary, Huang, Xianxi, additional, Hirsch, James, additional, Mehmi, Sanjeev, additional, Fonda, Holly, additional, Chan, Khin, additional, Huang, Ngan F., additional, Aalami, Oliver, additional, Froelicher, Victor F., additional, Lee, David P., additional, Myers, Jonathan, additional, Lee, Andrew S., additional, and Nguyen, Patricia K., additional

Published
2021
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42. We Are Thriving: Increasing the Number of Women in Engineering.

Author

Redmond, Kathryn E., Panther, Grace, Asadollahipajouh, Mojdeh, Kulesza, Stacey, and Liang, Grace

Subjects
WOMEN in engineering, ENGINEERING education in universities & colleges, EDUCATIONAL objectives, EDUCATIONAL outcomes, TEACHING models
Abstract

An ongoing focus of engineering education research is on increasing the number of women in engineering. Previous studies have primarily focused on examining why the number of women enrolled in engineering colleges remains persistently low. In doing so, while we have gained btter understanding of the challenges and barriers that women encountered and factors that contribute to such negative experiences, it also, as some scholars have pointed out, has cast a deficit frame on such matters. In this study, we take on a positive stand where we focus on women undergraduate students who not only "stay" but also succeed in engineering programs (that is, our definition of thriving) as a way to locate the personal and institutional factors that facilitate such positive outcomes. Our initial pilot study involved two female engineering undergraduate students at an R1 university. Each student was interviewed three times. While each of the interviews in the sequence had a slightly different focus, the overall goal was to understand the women's autobiographic and educational experiences leading to their paths to engineering and participation in the engineering project teams. The inductive thematic analysis revealed several primary findings which subsequently played a major role in developing a codebook for the current study. Building upon what is learned from the pilot study, the current study uses a layered multi-case study design involving three institutions: a public/private Ivy League and statutory land-grand research university in the Northeast, a public land-grant research university in the Midwest, and a public land-grant research university in the Southwest which is also designated as MSI/HSI. In addition to the interview method, data collection also contains documents and artifacts. For this paper, we zone in onto the data collected in the first interviews, known as the "life history" where we mainly learn about the women undergraduate participants' personal-familial contexts that contribute to their entry to majoring in engineering as identified by the women themselves. Preliminary findings indicate that: (1) our participants tend to have supportive families; (2) while all experienced gender biases, not everyone has formed a critical consciousness of sexism; and (3) being able to actually engage by "doing" something and creating a product is key to the women's finding joy in engineering and associating themself with the field/profession. It is important to note that the second interviews, which focus on the educational journey of the participants in relation to engineering identity development and project team experiences, are underway. The ultimate goal for the study is to develop a theoretical framework speaking to a multifaceted model of forces (micro as autobiographic, macro as institutional, and in-between or middle-level as team-based) in shaping women's entry and advance in engineering programs. This framework will recognize the variations in institutional type, resource availability, and structural and cultural characteristics and traditions in teams. It will also use such differences to show possibilities of more versatile ways for diversifying pathways for women and other minoritized groups to thrive in engineering. [ABSTRACT FROM AUTHOR]

Published
2022

46. The genetic architecture of the human cerebral cortex

Author

Grasby, Katrina L, Jahanshad, Neda, Shatokhina, Natalia, Mirza-Schreiber, Nazanin, Moreira, Jose C V, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M, Orfanos, Dimitri Papadopoulos, Pearson, John F, Zsembik, Leo C P, Pitcher, Toni L, Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M, Reay, William R, Redlich, Ronny, Reinbold, Céline S, Repple, Jonathan, Richard, Geneviève, Thomopoulos, Sophia I, Riedel, Brandalyn C, Risacher, Shannon L, Rocha, Cristiane S, Mota, Nina Roth, Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J, Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R, Zhu, Alyssa H, Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E, Sprooten, Emma, Tansey, Katherine E, Teumer, Alexander, Thalamuthu, Anbupalam, Strike, Lachlan T, Tordesillas-Gutiérrez, Diana, Turner, Jessica A, Uhlmann, Anne, Vallerga, Costanza Ludovica, van der Meer, Dennis, van Donkelaar, Marjolein M J, van Eijk, Liza, van Erp, Theo G M, van Haren, Neeltje E M, van Rooij, Daan, Agartz, Ingrid, van Tol, Marie-José, Veldink, Jan H, Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M, Wen, Wei, Westlye, Lars T, Whelan, Christopher D, Alhusaini, Saud, Witt, Stephanie H, Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L, Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P, Artiges, Eric, Almeida, Marcio A A, Assareh, Amelia A, Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L, Brown, Gregory G, Cichon, Sven, Curran, Joanne E, Davies, Gareth E, Degenhardt, Franziska, Dennis, Michelle F, Alnæs, Dag, Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P, Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A, Green, Robert C, Häusler, Alexander N, Heindel, Walter, Amlien, Inge K, Ho, Beng-Choon, Hoffmann, Wolfgang U, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R, Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A, Kolskår, Knut, Painter, Jodie N, Andersson, Micael, Koops, Sanne, Krug, Axel, Lim, Kelvin O, Luykx, Jurjen J, Mathalon, Daniel H, Mather, Karen A, Mattay, Venkata S, Matthews, Sarah, Mayoral Van Son, Jaqueline, McEwen, Sarah C, Ard, Tyler, Melle, Ingrid, Morris, Derek W, Mueller, Bryon A, Nauck, Matthias, Nordvik, Jan E, Nöthen, Markus M, O'Leary, Daniel S, Opel, Nils, Martinot, Marie-Laure Paillère, Pike, G Bruce, Armstrong, Nicola J, Preda, Adrian, Quinlan, Erin B, Rasser, Paul E, Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M, Tooney, Paul A, Torres, Fábio R, Veltman, Dick J, Voyvodic, James T, Ashley-Koch, Allison, Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H H, Bis, Joshua C, Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Atkins, Joshua R, Ikram, M Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L, Mazoyer, Bernard, Mosley, Thomas H, Roshchupkin, Gennady V, Satizabal, Claudia L, Schmidt, Reinhold, Seshadri, Sudha, Bernard, Manon, Yang, Qiong, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, Consortium, EPIGEN, Consortium, IMAGEN, Consortium, SYS, Initiative, Parkinson’s Progression Markers, Alvim, Marina K M, Ames, David, Anderson, Tim J, Brouwer, Rachel M, Andreassen, Ole A, Arias-Vasquez, Alejandro, Bastin, Mark E, Baune, Bernhard T, Beckham, Jean C, Blangero, John, Boomsma, Dorret I, Brodaty, Henry, Brunner, Han G, Buckner, Randy L, Buimer, Elizabeth E L, Buitelaar, Jan K, Bustillo, Juan R, Cahn, Wiepke, Cairns, Murray J, Calhoun, Vince, Carr, Vaughan J, Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L, Cendes, Fernando, Bülow, Robin, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C, Dannlowski, Udo, de Geus, Eco J C, Deary, Ian J, Delanty, Norman, Depondt, Chantal, Desrivières, Sylvane, Donohoe, Gary, Bürger, Christian, Espeseth, Thomas, Fernández, Guillén, Fisher, Simon E, Flor, Herta, Forstner, Andreas J, Francks, Clyde, Franke, Barbara, Glahn, David C, Gollub, Randy L, Grabe, Hans J, Colodro-Conde, Lucía, Cannon, Dara M, Gruber, Oliver, Håberg, Asta K, Hariri, Ahmad R, Hartman, Catharina A, Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A, Hillegers, Manon H J, Hoekstra, Pieter J, Holmes, Avram J, Chakravarty, Mallar, Hong, L Elliot, Hopkins, William D, Hulshoff Pol, Hilleke E, Jernigan, Terry L, Jönsson, Erik G, Kahn, René S, Kennedy, Martin A, Kircher, Tilo T J, Kochunov, Peter, Kwok, John B J, Chen, Qiang, Le Hellard, Stephanie, Loughland, Carmel M, Martin, Nicholas G, Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L, Meyer-Lindenberg, Andreas, Michie, Patricia T, Morey, Rajendra A, Mowry, Bryan, Cheung, Joshua W, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A, Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Polderman, Tinca J C, Posthuma, Danielle, Rietschel, Marcella, Couvy-Duchesne, Baptiste, Roffman, Joshua L, Rowland, Laura M, Sachdev, Perminder S, Sämann, Philipp G, Schall, Ulrich, Schumann, Gunter, Scott, Rodney J, Sim, Kang, Sisodiya, Sanjay M, Smoller, Jordan W, Dale, Anders M, Sommer, Iris E, St Pourcain, Beate, Stein, Dan J, Toga, Arthur W, Trollor, Julian N, Van der Wee, Nic J A, van 't Ent, Dennis, Völzke, Henry, Walter, Henrik, Weber, Bernd, Dalvie, Shareefa, Weinberger, Daniel R, Wright, Margaret J, Zhou, Juan, Stein, Jason L, Thompson, Paul M, Medland, Sarah E, Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis, Witte, A Veronica, Darin, Abigail, Fleisher, Adam, de Araujo, Tânia K, Pierce, Aimee, Mintz, Akiva, Lerner, Alan, Reith, Alastair D, Hofman, Albert, Espay, Alberto, Ihlenfeld, Albrecht, Ing, Alex, Iranzo, Alex, Beiser, Alexa S, de Zubicaray, Greig I, Norbash, Alexander, Barbot, Alexis, Rudolph, Alice, Portillo, Alicia, Chalker, Alison, Levey, Allan I, Rosen, Allyson, Smith, Amanda, Catafau, Ana, de Zwarte, Sonja M C, Ulysse, Anaztasia, Uitterlinden, André G, Becker, Andreas, Budson, Andrew E, Kertesz, Andrew, Siderowf, Andrew, Bralten, Janita, den Braber, Anouk, Singleton, Andrew, James, Angela, Oliver, Angela, Mishra, Aniket, Hake, Ann Marie, Burke, Anna, Sarrael, Antero, Porsteinsson, Anton P, Stringaris, Argyris, McCoy, Arita, Doan, Nhat Trung, Villringer, Arno, Lenahan, Art, Toga, Arthur, Bokde, Arun, Rawlins, Ashlee, Lamb, Ashley, Lee, Athena, Raj, Balebail Ashok, Tran, Baochan, Dohm, Katharina, Ruggeri, Barbara, Saba, Barbara, Lane, Barton, Yanez, Beatriz, Ances, Beau, Dunlop, Becky, Mudge, Benita, Ravina, Bernard, Ittermann, Bernd, Ehrlich, Stefan, van Noort, Betteke, Lind, Betty, Shah, Bina, Stefanovic, Bojana, Goldstein, Bonnie S, Bonakdarpour, Borna, Matthews, Brandy R, Borowski, Bret, Ott, Brian R, Reynolds, Brigid, Engelbrecht, Hannah-Ruth, Mollenhauer, Brit, Miller, Bruce L, Psaty, Bruce M, Spann, Bryan M, Sadowsky, Carl, Linder, Carly, Franz, Carol E, Tanner, Caroline, Kopil, Catherine, Thomas, Cathi-Ann, Erk, Susanne, Ward, Chad, Bernick, Charles, Smith, Charles D, DeCarli, Charles, Caspell, Chelsea, Deeley, Cheryl, Riordan, Cheryl, Mathis, Chet, Onyike, Chiadi, Heyn, Chris Chinthaka, Fan, Chun Chieh, Hosein, Chris, Leach, Christi, Bÿchel, Christian, Gigliotti, Christina, Hunter, Christine, Belden, Christine M, Tzourio, Christophe, Coffey, Christopher, van Dyck, Christopher H, Clark, Christopher M, Fedko, Iryna O, Wu, Chuang-Kuo, Albers, Colleen S, Chu, Congying, Brand, Connie, Isensee, Corinna, van Duijn, Cornelia M, Bishop, Courtney, Bodge, Courtney, Foley, Sonya F, Tatsuoka, Curtis, Casaceli, Cynthia, Carlsson, Cynthia M, Mathews, Dana, D'Agostino, Daniel, Silverman, Daniel H S, Marson, Daniel, Berg, Daniela, Harvey, Danielle, Jennings, Danna, Ford, Judith M, Wolk, David A, Goldstein, David B, Bachman, David, Brooks, David, Clark, David, Geldmacher, David, Hart, David, Holtzman, David, Jones, David, Hibar, Derrek P, Fukunaga, Masaki, Knopman, David, Hewitt, David L, Perry, David, Russell, David, Standaert, David, Winkfield, David, Green, Davis Robert C, Fontaine, Deborah, Miller, Delwyn D, Gessert, Devon, Garrett, Melanie E, Kerwin, Diana, Willeke, Diana, Drost, Dick, Papadopoulos, Dimitri, Rowe, Dominic, Simpson, Donna M, Muni, Donna, Galasko, Douglas, Scharre, Douglas W, Fillmer, Ariane, Ge, Tian, Bartha, Rob, Celmins, Dzintra, Zimmerman, Earl A, Teng, Edmond, Tolosa, Eduardo, Coleman, Edward, Zamrini, Edward, Mitsis, Effie, Finger, Elizabeth, Giddaluru, Sudheer, Oates, Elizabeth, Sosa, Elizabeth, Woo, Ellen, Rogalski, Emily, Lethbridge, Emma, Dooley, Eoin, Foster, Eric, Reiman, Eric M, Quinlan, Erin Burke, Goldman, Aaron L, Franklin, Erin, Heinzen, Erin L, Fletcher, Evan, Sprenger, Fabienne, Crivello, Fabrice, Biondo, Francesca, Parfitt, Francine, Hefti, Franz, Beyer, Frauke, Nees, Frauke, Green, Melissa J, Leonard, Gabriel, Robert, Gabriel, Thai, Gaby, Marshall, Gad A, Barker, Gareth, Conrad, Gary, Tremont, Geoffrey, Bartzokis, George, Groenewold, Nynke A, Hsiung, Ging-Yuek Robin, Malferrari, Giulia, Chiang, Gloria, Pearlson, Godfrey D, Liang, Grace, Jicha, Greg, Sorensen, Greg, Todd, Gretchen, Jimenez, Gustavo, Grotegerd, Dominik, Zare, Habil, Grabe, Hans Jörgen, Vanderswag, Helen, Schmidt, Helena, Venkov, Heli, Lemaitre, Hervé, Gurholt, Tiril P, Grossman, Hillel, Shill, Holly, Soares, Holly, Lin, Honghuang, Capote, Horacio, Bergman, Howard, Chertkow, Howard, Feldman, Howard, Fillit, Howard, Rosen, Howard J, Gutman, Boris A, Koleva, Hristina, Fernandez, Hubert, Garavan, Hugh, Shim, Hyungsub, Grachev, Igor D, Richard, Irene, Filippi, Irina, Rachinsky, Irina, Wurster, Isabel, Lind, Penelope A, Hansell, Narelle K, Mintzer, Jacobo, Ziolkowski, Jaimie, Brewer, James, Lah, James J, Leverenz, James, Becker, James T, Tetrud, James, Singleton-Garvin, Jamika, Egebjerg, Jan, Cellar, Janet S, Harris, Mathew A, Pentilla, Jani, Brosch, Jared R, Tinklenberg, Jared, Karlawish, Jason H, Meyer, Javier Villanueva, Himali, Jayandra J, Poline, Jean-Baptiste, Gunter, Jeff, Kaye, Jeffrey A, Harrison, Marc B, Dalley, Jeffrey, Burns, Jeffrey M, Petrella, Jeffrey R, Mule, Jennifer, Salazar, Jennifer, Rotter, Jerome I, Yesavage, Jerome, Cedarbaum, Jesse, Jiang, Jiyang, Haswell, Courtney C, Allard, Joanne, Lord, Joanne L, Hetelle, Joel, Kwok, John B, Brockington, John, Morris, John C, Hsiao, John, Morris, John, Olichney, John, Trojanowki, John Q, Hauser, Michael, Rogers, John, Seibyl, John, Yankey, Jon, Dubow, Jordan S, Jankovic, Joseph, Quinn, Joseph, Kass, Joseph S, Taylor, Joy L, Heidebrink, Judith L, Herms, Stefan, Trollor, Julian, Fröhner, Juliane, Anderson, Karen, Blank, Karen, Crawford, Karen, Smith, Karen Ekstam, Bell, Karen L, Williams, Karen, Kieburtz, Karl, Heslenfeld, Dirk J, Gauss, Katharina, Gloer, Katherine, Johnson, Kathleen, Tingus, Kathleen, DeMarco, Kathryn, Sink, Kaycee M, Hawkins, Keith A, Johnson, Keith A, Kantarci, Kejal, Ho, New Fei, Faber, Kelley, Harless, Kelly, Makino, Kelly M, Marek, Kenneth, Spicer, Kenneth, Shianna, Kevin, Chen, Kewei, Nam, Ki Won, Martin, Kim, Poki-Walker, Kim, Hoehn, David, Seppi, Klaus, Johnson, Kris, Fargher, Kristin, Lipowski, Kristine, Espay, Kristy, Womack, Kyle, Chahine, Lama, Flashman, Laura A, Daedelow, Laura, Hoffmann, Per, Leary, Laura, Beckett, Laurel, Honig, Lawrence S, Thal, Leon, Shaw, Leslie M, Kuller, Lew, Apostolova, Liana, Teodoro, Liberty, Rees, Linda, Pizzagalli, Fabrizio, Holleran, Laurena, Lewis, Lindsay, Hergesheimer, Lindsey, Silbert, Lisa C, Ravdin, Lisa, Taylor-Reinwald, Lisa, Uribe, Liz, Schneider, Lon S, Daiello, Lori A, Richer, Louis, Poustka, Luise, Hoogman, Martine, Pirpamer, Lukas, Mesulam, M Marcel, Ismail, M Saleem, Ranola, Madelaine, Korecka, Magdalena, Raichle, Marc, Seltzer, Marc, van der Brug, Marcel, Hottenga, Jouke-Jan, Mesulam, Marek-Marsel, Carrillo, Maria, Carroll, Maria, Knol, Maria J, Kataki, Maria, Greig-Custo, Maria T, Paillere, Marie-Laure, Albert, Marilyn, Love, Marissa Natelson, Ikeda, Masashi, Mintun, Mark A, Frasier, Mark, Logue, Mark, Minton, Mark, Loeffler, Markus, Scholz, Markus, Baca, Marne, Farlow, Martin R, Sadowski, Martin, Janowitz, Deborah, Creech, Mary L, Hynes, Mary L, Quiceno, Mary, Oakley, MaryAnn, Harris, Mat, Senjem, Matt, Bernstein, Matthew, Panizzon, Matthew S, Stern, Matthew, Becerra, Mauricio, Jansen, Iris E, Witbracht, Megan, Vernooij, Meike W, Brandabur, Melanie, Keltz, Melanie, Lamar, Melissa, Yang, Mia, Ahlijanian, Michael, Borrie, Michael, Neale, Michael C, Donohue, Michael, Jia, Tianye, Lyons, Michael J, Lin, Michael, Rapp, Michael, Smolka, Michael, Weiner, Michael W, Weiner, Michael, Figurski, Michal, Perron, Michel, Assaly, Michele, Luciano, Michelle, Jockwitz, Christiane, Rainka, Michelle, Dang, Mimi, Sheikh, Mohammed O, Ghanbari, Mohsen, Gaikwad, Mrunalini, Chowdhury, Munir, Trncic, Nadira, Amin, Najaf, Johnson, Nancy, Kanai, Ryota, Kowalksi, Nancy, Monahan, Nancy, Gillespie, Nathan A, Pacini, Nathaniel, Buckholtz, Neil, Kowall, Neil, Graff-Radford, Neill R, Fox, Nick, Pavese, Nicola, Karama, Sherif, Cairns, Nigel J, Schuff, Norbert, Foster, Norm, Relkin, Norman, Oyonumo, Ntekim E, Pomara, Nunzio, James, Olga, Ogunlana, Olu, Ching, Christopher R K, Kasperaviciute, Dalia, Carmichael, Owen, Doraiswamy, P Murali, Casalin, Paola, Barone, Paolo, Fatica, Parianne, Conrod, Patricia, Johnson, Patricia Lynn, Samuels, Patricia, Aisen, Paul, Malloy, Paul, Kaufmann, Tobias, Thompson, Paul, Ogrocki, Paula, Bezivin-Frere, Pauline, Maillard, Pauline, Fontoura, Paulo, Taylor, Peggy, Hogarth, Penelope, Gowland, Penny, Davies, Peter, Kelly, Sinead, Hardy, Peter, Snyder, Peter J, Snyder, Peter, Amouyel, Philippe, Muglia, Pierandrea, Tariot, Pierre, Lu, Po H, Varma, Pradeep, Vemuri, Prashanthi, Kikuchi, Masataka, Doody, Rachelle S, Carter, Raina, Shah, Raj C, Griffith, Randall, Yeh, Randy, Duara, Ranjan, Tarawneh, Rawan, James, Raymond, Turner, Raymond Scott, Klein, Marieke, Hernando, Raymundo, Silverstein, Rebecca, Sperling, Reisa A, Wilson, Renee, Carson, Richard E, Frank, Richard, El Khouli, Riham, Koeppe, Robert A, Santulli, Robert B, Knapp, Michael, Hauser, Robert, Umek, Robert, Radtke, Rodney, Killiany, Ronald, Petersen, Ronald, Rodriguez, Rosemarie, Miranda, Ruben, Knodt, Annchen R, Bruehl, Ruediger, Xia, Rui, Swerdlow, Russell H, Ottmann, Ruth, Millenet, Sabina, Borges-Neto, Salvador, Frank, Samuel, Black, Sandra, Weintraub, Sandra, Obradov, Sanja, Krämer, Bernd, Asthana, Sanjay, Vaishnavi, Sanjeev, Dolen, Sara, Mason, Sara S, Hohmann, Sarah, Kremen, Sarah, Miller, Sarah, Walter, Sarah, Herring, Scott, Neu, Scott, Lam, Max, Aydin, Semiha, Ahmad, Shahzad, Harlan, Sherry, Sirrel, Sherye A, Lasch, Shirley, Hu, Shu-Ching, Li, Shuo, Kittur, Smita, Chowdhury, Sohini, Lancaster, Thomas M, Pawluczyk, Sonia, Maingault, Sophie, Schneider, Stacy, Seiler, Stephan, Guthrie, Stephanie, Kielb, Stephanie, Reeder, Stephanie, Correia, Stephen, Pasternak, Stephen, McMahon, Mary Agnes B, Lee, Phil H, Salloway, Stephen, Johnson, Sterling, Williams, Steve, Chao, Steven, Arnold, Steven E, Paul, Steven, Potkin, Steven, Factor, Stewart, Isaacson, Stuart, Lett, Tristram A, Kim, Sungeun, Ainscough, Susan, Schultz, Susan K, Landau, Susan, Mendick, Susan, Rountree, Susan, Ostrowizki, Suzanne, Veillette, Suzanne, van der Lee, Sven J, Desrivieres, Sylvane, Lewis, Lindsay B, Lee, T-Y, Simuni, Tanya, Foroud, Tatiana, Foroud, Tatiana M, Wong, Terence Z, Villena, Teresa, Comery, Thomas, Obisesan, Thomas O, Lopes-Cendes, Iscia, Banaschewski, Tobias, Sherer, Todd, Montine, Tom, Paus, Tomáš, Robbins, Trevor, Bromberg, Uli, Völker, Uwe, Pavlik, Valory, Arnedo, Vanessa, Kiyasova, Vera, Bates, Vernice, Logovinsky, Veronika, Sossi, Vesna, Shibley, Victoria, Frouin, Vincent, Lee, Virginia, Poewe, Werner, Jagust, William, Brooks, William M, Macciardi, Fabio, Pavlosky, William, Potter, William, Kremen, William S, Longstreth, William T, Niessen, Wiro J, Jian, Xueqiu, Stern, Yaakov, Saba, Yasaman, Cabrera, Yuliana, Grimmer, Yvonne, Marquand, Andre F, Khachaturian, Zaven, Mari, Zoltan, Mathias, Samuel R, Melzer, Tracy R, Milaneschi, Yuri, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium, SYS Consortium, Parkinson’s Progression Markers Initiative, Stochastics, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Science and Society, Cognitive Psychology, IBBA, APH - Personalized Medicine, Complex Trait Genetics, APH - Methodology, Clinical Neuropsychology, Sociology and Social Gerontology, Amsterdam Neuroscience - Complex Trait Genetics, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), Neurology, Psychiatry, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Human genetics, APH - Digital Health, Psychology, Precision Medicine Institute of Psychiatry, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Clinical Genetics, Epidemiology, Medical Informatics, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neurodegeneratives Diseases Institute (IMN-UMR CNRS 5293), Centre National de la Recherche Scientifique (CNRS), General Paediatrics, ARD - Amsterdam Reproduction and Development, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Brain mapping, 0302 clinical medicine, Cognition, Cortex (anatomy), ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, 0303 health sciences, Brain Mapping, Multidisciplinary, COMMON VARIANTS, Parkinson Disease, Organ Size, Central sulcus, Magnetic Resonance Imaging, medicine.anatomical_structure, Cerebral cortex, Neuroinformatics, EXPRESSION, endocrine system, central sulcus, SURFACE-AREA, Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, medicine, Attention deficit hyperactivity disorder, Humans, General, Gene, METAANALYSIS, 030304 developmental biology, Progenitor, CORTICAL SULCI, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Genetic variants, Genetic Variation, Attention Deficit Disorder with Hyperactivity, Genetic Loci, Genome-Wide Association Study, functional annotation, medicine.disease, Genetic architecture, 030104 developmental biology, Evolutionary biology, OBSERVER-INDEPENDENT CHARACTERIZATION, Multiple comparisons problem, ddc:320, genome-wide association, Neuroscience, 030217 neurology & neurosurgery
Abstract

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group., The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020

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