Tags

Type your tag names separated by a space and hit enter

Association of Parkinson disease risk loci with mild parkinsonian signs in older persons.
JAMA Neurol. 2014 Apr; 71(4):429-35.JN

Abstract

IMPORTANCE

Parkinsonian motor signs are common in the aging population and are associated with adverse health outcomes. Compared with Parkinson disease (PD), potential genetic risk factors for mild parkinsonian signs have been largely unexplored.

OBJECTIVE

To determine whether PD susceptibility loci are associated with parkinsonism or substantia nigra pathology in a large community-based cohort of older persons.

DESIGN, SETTING, AND PARTICIPANTS

Eighteen candidate single-nucleotide polymorphisms from PD genome-wide association studies were evaluated in a joint clinicopathologic cohort. Participants included 1698 individuals and a nested autopsy collection of 821 brains from the Religious Orders Study and the Rush Memory and Aging Project, 2 prospective community-based studies.

MAIN OUTCOMES AND MEASURES

The primary outcomes were a quantitative measure of global parkinsonism or component measures of bradykinesia, rigidity, tremor, and gait impairment that were based on the motor Unified Parkinson's Disease Rating Scale. In secondary analyses, we examined associations with additional quantitative motor traits and postmortem indices, including substantia nigra Lewy bodies and neuronal loss.

RESULTS

Parkinson disease risk alleles in the MAPT (rs2942168; P = .0006) and CCDC62 (rs12817488; P = .004) loci were associated with global parkinsonism, and these associations remained after exclusion of patients with a PD diagnosis. Based on motor Unified Parkinson's Disease Rating Scale subscores, MAPT (P = .0002) and CCDC62 (P = .003) were predominantly associated with bradykinesia, and we further discovered associations between SREBF1 (rs11868035; P = .005) and gait impairment, SNCA (rs356220; P = .04) and rigidity, and GAK (rs1564282; P = .03) and tremor. In the autopsy cohort, only NMD3 (rs34016896; P = .03) was related to nigral neuronal loss, and no associations were detected with Lewy bodies.

CONCLUSIONS AND RELEVANCE

In addition to the established link to PD susceptibility, our results support a broader role for several loci in the development of parkinsonian motor signs and nigral pathology in older persons.

Authors+Show Affiliations

Department of Neurology, Baylor College of Medicine, Houston, Texas2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas3Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston.Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, Illinois.Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.Program in Translational Neuropsychiatric Genomics, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts7Harvard Medical School, Boston, Massachusetts8Program in Medical and Population Genetics, Broad Institute, Cam.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24514572

Citation

Shulman, Joshua M., et al. "Association of Parkinson Disease Risk Loci With Mild Parkinsonian Signs in Older Persons." JAMA Neurology, vol. 71, no. 4, 2014, pp. 429-35.
Shulman JM, Yu L, Buchman AS, et al. Association of Parkinson disease risk loci with mild parkinsonian signs in older persons. JAMA Neurol. 2014;71(4):429-35.
Shulman, J. M., Yu, L., Buchman, A. S., Evans, D. A., Schneider, J. A., Bennett, D. A., & De Jager, P. L. (2014). Association of Parkinson disease risk loci with mild parkinsonian signs in older persons. JAMA Neurology, 71(4), 429-35. https://doi.org/10.1001/jamaneurol.2013.6222
Shulman JM, et al. Association of Parkinson Disease Risk Loci With Mild Parkinsonian Signs in Older Persons. JAMA Neurol. 2014;71(4):429-35. PubMed PMID: 24514572.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Parkinson disease risk loci with mild parkinsonian signs in older persons. AU - Shulman,Joshua M, AU - Yu,Lei, AU - Buchman,Aron S, AU - Evans,Denis A, AU - Schneider,Julie A, AU - Bennett,David A, AU - De Jager,Philip L, PY - 2014/2/12/entrez PY - 2014/2/12/pubmed PY - 2014/6/10/medline SP - 429 EP - 35 JF - JAMA neurology JO - JAMA Neurol VL - 71 IS - 4 N2 - IMPORTANCE: Parkinsonian motor signs are common in the aging population and are associated with adverse health outcomes. Compared with Parkinson disease (PD), potential genetic risk factors for mild parkinsonian signs have been largely unexplored. OBJECTIVE: To determine whether PD susceptibility loci are associated with parkinsonism or substantia nigra pathology in a large community-based cohort of older persons. DESIGN, SETTING, AND PARTICIPANTS: Eighteen candidate single-nucleotide polymorphisms from PD genome-wide association studies were evaluated in a joint clinicopathologic cohort. Participants included 1698 individuals and a nested autopsy collection of 821 brains from the Religious Orders Study and the Rush Memory and Aging Project, 2 prospective community-based studies. MAIN OUTCOMES AND MEASURES: The primary outcomes were a quantitative measure of global parkinsonism or component measures of bradykinesia, rigidity, tremor, and gait impairment that were based on the motor Unified Parkinson's Disease Rating Scale. In secondary analyses, we examined associations with additional quantitative motor traits and postmortem indices, including substantia nigra Lewy bodies and neuronal loss. RESULTS: Parkinson disease risk alleles in the MAPT (rs2942168; P = .0006) and CCDC62 (rs12817488; P = .004) loci were associated with global parkinsonism, and these associations remained after exclusion of patients with a PD diagnosis. Based on motor Unified Parkinson's Disease Rating Scale subscores, MAPT (P = .0002) and CCDC62 (P = .003) were predominantly associated with bradykinesia, and we further discovered associations between SREBF1 (rs11868035; P = .005) and gait impairment, SNCA (rs356220; P = .04) and rigidity, and GAK (rs1564282; P = .03) and tremor. In the autopsy cohort, only NMD3 (rs34016896; P = .03) was related to nigral neuronal loss, and no associations were detected with Lewy bodies. CONCLUSIONS AND RELEVANCE: In addition to the established link to PD susceptibility, our results support a broader role for several loci in the development of parkinsonian motor signs and nigral pathology in older persons. SN - 2168-6157 UR - https://www.unboundmedicine.com/medline/citation/24514572/Association_of_Parkinson_disease_risk_loci_with_mild_parkinsonian_signs_in_older_persons_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2013.6222 DB - PRIME DP - Unbound Medicine ER -