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Review Article

Clinicogenetics of Parkinson’s disease: a

drawing but not completed picture

1
Chao‑Dong Wang , Piu Chan 2
1 Department of Neurology, The Affiliated Sanming First Hospital, Fujian Medical University, Sanming 365000, Fujian, China.
2 Department of Neurobiology and Neurology, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Xuanwu
Hospital of Capital Medical University, Beijing 100053, China.

ABSTRA CT
Parkinson’s disease (PD) is a prevalent neurodegenerative disorder mainly affecting the population over the age of 60 years. The
past decade has seen rapidly emerging data supporting a major importance of genetic factors in the development of PD. Increasing
number of large‑scale and replicating association studies has facilitated the confirmation of the possible predisposing factors to
PD and the selection of genetic variants for risk prediction. While evidences are accumulating that variations within the SNCA,
LRRK2, MAPT and GBA genes increase the individuals’ vulnerability to PD, inconclusive or negative results have been reported
for an association between PD and variants of the parkin, PINK1, DJ‑1, UCH‑L1, Omi/HtrA2, GIGYF2, PLA2G6, VPS35, EIF4G1
and BST1 genes. However, our understanding of the genetic picture of PD remains preliminary. Molecular diagnosis of the disease
is only recommended for cases with clear family history, and currently, there is no ideal genomic biomarker available to predict the
disease onset and progression, or to make a molecular classification of the disease. Efforts are expected to identify more genetic
predisposing factors and to further clarify their roles in the mechanisms of PD.

Key words: Association, biomarkers, genetic variants, Parkinson’s disease

INTRODUCTION One important conceptual update of the genetic
profiling of PD is that mutations or variations within
Parkinson’s disease (PD) is a prevalent neurodegenerative causative genes for a minority of monogenic familial
disorder affecting 1-2% of the population over the age of PD are also associated with sporadic PD. Studies in
60 years. The disease results mainly from progressive PD families have identified 11 (a‑synuclein, parkin,
[1]
and profound degeneration of dopaminergic neurons UCH‑L1, PINK1, DJ‑1, LRRK2, ATP13A2, OMI/HTRA2,
in the substantia nigra with the presence of Lewy FBX07, VPS35, EIF4G1) causative genes and 4 loci of
bodies containing aggregates of α-synuclein and other linkage across the genome (PARK3, PARK10, PARK12
substances. [2,3] Although the etiology and mechanisms of and PARK16) pending characterization. Analysis
PD remain largely unclear, the development of the disease of mutations or variations in many of these genes
is believed to be the combined results of three interactive has been performed in recent years among diverse
events: genetic susceptibility, environmental exposures ethnic populations. In addition, the newly emerged
and the aging process. [4-8] The relative role of genetic genome-wide association studies (GWAS) have been
and environmental factors has been debated for many used to identify novel genetic associations with the
years, however, evidences are rapidly accumulating disease at the whole-genome level. [12-15] More recent
that genetic risk factors are of major importance in the progress has been made by the powerful technique
sporadic form of the disease, accounting for at least 10% of next-generation sequencing. [16,17] Further, more
of the general PD population. [1,9-11] and more large-scale and multi-center collaborative
analyses have been completed thanks to the improving
Access this article online analytic tools and the increasingly close international
Quick Response Code: cooperation. The results published so far are consistent
Website: or conflicting with each other, reflecting confirmative,
www.nnjournal.net
inconclusive or negative associations between genetic
DOI: variants and PD. In this review, we give an up-to-date
10.4103/2347-8659.143662 view of the genes that may have associations with
the risk for PD and their implications in clinical

Corresponding Author: Dr. Chao‑Dong Wang, Department of Neurology, The Affiliated Sanming First Hospital, Fujian Medical
University, Dongxin 1 Road, Liedong Street, Sanming 365000, Fujian, China. E‑mail: cdongwang01@126.com
st

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