TY - JOUR
T1 - Association of MAPT subhaplotypes with clinical and demographic features in Parkinson’s disease
AU - Deutschlander, Angela B.
AU - Konno, Takuya
AU - Soto-Beasley, Alexandra I.
AU - Walton, Ronald L.
AU - van Gerpen, Jay A.
AU - Uitti, Ryan J.
AU - Heckman, Michael G.
AU - Wszolek, Zbigniew K.
AU - Ross, Owen A.
N1 - Funding Information:
The study was supported by the Mayo Clinic American Parkinson Disease Association (APDA) Mayo Clinic Information and Referral Center, an APDA Center for Advanced Research, the Mayo Clinic Lewy Body Dementia Association (LBDA) Research Center of Excellence, Mayo Clinic functional genomics of LBD program and an NINDS Lewy body dementia Center WithOut Walls (U54 NS110435).
Funding Information:
The study was supported by the Mayo Clinic American Parkinson Disease Association (APDA) Mayo Clinic Information and Referral Center, an APDA Center for Advanced Research, the Mayo Clinic Lewy Body Dementia Association (LBDA) Research Center of Excellence, Mayo Clinic functional genomics of LBD program and an NINDS Lewy body dementia Center WithOut Walls (U54 NS110435). Mayo Clinic is an American Parkinson Disease Association (APDA) Mayo Clinic Information and Referral Center, an APDA Center for Advanced Research, the Mayo Clinic Lewy Body Dementia Association (LBDA) Research Center of Excellence, Mayo Clinic functional genomics of LBD program and an NINDS Lewy body dementia Center WithOut Walls (U54 NS110435). OAR is supported by the National Institutes of Health (NIH; R01 NS78086; U54 NS100693), the US Department of Defense (W81XWH-17-1-0249), The Little Family Foundation, the Mayo Clinic Center for Individualized Medicine, and the Michael J. Fox Foundation. A. B. Deutschlander is supported by Allergan, Inc. (educational grant), by a gift from Carl Edward Bolch, Jr, and Susan Bass Bolch, and by the Sol Goldman Charitable Trust. T. Konno received research support from JSPS Overseas Research Fellowships. Z. K. Wszolek is supported by the NIH, Mayo Clinic Center for Regenerative Medicine, the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch, The Sol Goldman Charitable Trust, and Donald G. and Jodi P. Heeringa. We thank Audrey Strongosky for assisting with data acquisition. We thank all patients for participation in the study.
Funding Information:
Mayo Clinic is an American Parkinson Disease Association (APDA) Mayo Clinic Information and Referral Center, an APDA Center for Advanced Research, the Mayo Clinic Lewy Body Dementia Association (LBDA) Research Center of Excellence, Mayo Clinic functional genomics of LBD program and an NINDS Lewy body dementia Center WithOut Walls (U54 NS110435). OAR is supported by the National Institutes of Health (NIH; R01 NS78086; U54 NS100693), the US Department of Defense (W81XWH‐17‐1‐0249), The Little Family Foundation, the Mayo Clinic Center for Individualized Medicine, and the Michael J. Fox Foundation. A. B. Deutschlander is supported by Allergan, Inc. (educational grant), by a gift from Carl Edward Bolch, Jr, and Susan Bass Bolch, and by the Sol Goldman Charitable Trust. T. Konno received research support from JSPS Overseas Research Fellowships. Z. K. Wszolek is supported by the NIH, Mayo Clinic Center for Regenerative Medicine, the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch, The Sol Goldman Charitable Trust, and Donald G. and Jodi P. Heeringa. We thank Audrey Strongosky for assisting with data acquisition. We thank all patients for participation in the study.
Publisher Copyright:
© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Objective: To determine whether distinct microtubule-associated protein tau MAPT H1 subhaplotypes are associated with clinical and demographic features in Parkinson’s disease. Methods: A retrospective cohort study included 855 unrelated Caucasian patients with Parkinson’s disease who were seen by Movement Disorder specialists at the Mayo Clinic Florida between 1998 and 2016. The primary outcome measures were specific demographic and clinical features of Parkinson’s disease, including age at onset, disease progression, survival, motor signs, dementia, dystonia, dyskinesia, autonomic dysfunction, impulse control disorder, psychiatric features, REM sleep behavior disorder, restless legs syndrome, and Parkinson’s disease subtype. Specific clinical features were measured at the initial visit and most recent visit. These outcomes were assessed for association with MAPT H1 subhaplotypes, which were defined by six haplotype tagging variants. Results: Median onset age was 64 years (range: 22-94 years); 548 (64%) of patients were male. Significant associations (P < 0.0029) were observed between MAPT H1b and orthostatic hypotension (OR = 1.72, P = 0.001); between H1j and rest tremor (OR = 0.15; P < 0.001) as well as REM sleep behavior disorder (OR = 3.87, P < 0.001); between H1r and bradykinesia (OR = 0.11; P < 0.001); and between H1v and restless legs syndrome (OR = 4.02, P = 0.002). Interpretation: Four MAPT H1 subhaplotypes, but not the H2 haplotype, were significantly associated with specific clinical features in Parkinson’s disease. MAPT haplotypic structure may explain some of the phenotypic variability in disease. Replication of our findings will be critical to fully resolve the Parkinson’s disease risk association signal at Chr17q21.
AB - Objective: To determine whether distinct microtubule-associated protein tau MAPT H1 subhaplotypes are associated with clinical and demographic features in Parkinson’s disease. Methods: A retrospective cohort study included 855 unrelated Caucasian patients with Parkinson’s disease who were seen by Movement Disorder specialists at the Mayo Clinic Florida between 1998 and 2016. The primary outcome measures were specific demographic and clinical features of Parkinson’s disease, including age at onset, disease progression, survival, motor signs, dementia, dystonia, dyskinesia, autonomic dysfunction, impulse control disorder, psychiatric features, REM sleep behavior disorder, restless legs syndrome, and Parkinson’s disease subtype. Specific clinical features were measured at the initial visit and most recent visit. These outcomes were assessed for association with MAPT H1 subhaplotypes, which were defined by six haplotype tagging variants. Results: Median onset age was 64 years (range: 22-94 years); 548 (64%) of patients were male. Significant associations (P < 0.0029) were observed between MAPT H1b and orthostatic hypotension (OR = 1.72, P = 0.001); between H1j and rest tremor (OR = 0.15; P < 0.001) as well as REM sleep behavior disorder (OR = 3.87, P < 0.001); between H1r and bradykinesia (OR = 0.11; P < 0.001); and between H1v and restless legs syndrome (OR = 4.02, P = 0.002). Interpretation: Four MAPT H1 subhaplotypes, but not the H2 haplotype, were significantly associated with specific clinical features in Parkinson’s disease. MAPT haplotypic structure may explain some of the phenotypic variability in disease. Replication of our findings will be critical to fully resolve the Parkinson’s disease risk association signal at Chr17q21.
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U2 - 10.1002/acn3.51139
DO - 10.1002/acn3.51139
M3 - Article
C2 - 32767721
AN - SCOPUS:85089065686
VL - 7
SP - 1557
EP - 1563
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
SN - 2328-9503
IS - 9
ER -