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Association of rare PPARGC1A variants with Parkinson’s disease risk

Abstract

Background

Recent researches on Parkinson’s disease (PD) pathogenesis discovered the correlation between PD and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) dysfunction and reduction of PPARGC1A gene expression. Hence, we detected PPARGC1A rare variants to clarify their effect on PD risk in a large population of PD patients in mainland China.

Methods

We applied whole-exome sequencing (WES) to 1917 patients with early-onset or familial PD and 1652 controls (WES cohort), and whole-genome sequencing (WGS) to 1962 patients with sporadic late-onset PD and 1279 controls (WGS cohort). To identify PPARGC1A rare variants, we used burden analysis to assess the relationship between PPARGC1A rare variants and PD susceptibility.

Results

30 rare missense variants in the cohort WES and 21 missense variants in the cohort WGS have been detected in the study and PPARGC1A missense variants are significantly associated with early-onset and familial PD susceptibility in our study (P = 0.012), which supports evidence that PPARGC1A rare variants are involved in the onset of early-onset and familial PD.

Conclusions

The study suggested that PPARGC1A rare variants may contribute to the risk of early-onset and familial PD.

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Fig. 1

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all patients and healthy individuals for permitting us to publish their information. This study was supported by the National key R&D projects (Grant No. 2021YFC2501204) and Key Project of Hunan Provincial Science and Technology Department (Grant No. 2021SK1011) to JG, Hunan Province Innovative Construction Project (No.2019SK2335) and Science and Technology Major Project of Hunan Provincial Science and Technology Department (Grant No. 2021SK1010) to JG, the Central Public-Interest Scientific Institution Basal Research Fund of Chinese Academy of Medical Sciences (Grant No.2018-12M-HL-025) to JG, the National Natural Science Foundation of China (Grant Nos. 81873785; 81974202; 82071439; U20A20355; 82001359) to JG and BT, and the innovative team program from Department of Science & Technology of Hunan Province (Grant No. 2019RS1010, No. 2020RC4043) to JG, and the Innovation-driven Team Project from Central South University (Grant No. 2020CX016) to JG, and the National key R&D projects (Grant No. 2021YFC2502100) to JL. We are also grateful for resources from the High-Performance Computing Center of Central South University.

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Authors and Affiliations

Authors

Contributions

L-ZL: Conceptualization, Methodology, Writing - original draft. YZ: Data curation, Formal analysis, Methodology, Writing - review & editing. HP: Data curation, Writing - review & editing. YX: Data curation, Writing - review & editing. YW: Data curation, Writing - review & editing. QX: Data curation, Funding acquisition. XY: Data curation, Funding acquisition. JT: Data curation, Funding acquisition. JL: Funding acquisition, Writing - review & editing. BT: Project administration, Supervision, Funding acquisition, Writing - review & editing. JG: Project administration, Supervision, Funding acquisition, Writing - review & editing.

Corresponding author

Correspondence to Ji-feng Guo.

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The study was approved by the Ethics Committee of Xiangya Hospital, Central South University and followed the Declaration of Helsinki.

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Li, Lz., Zhao, Yw., Pan, Hx. et al. Association of rare PPARGC1A variants with Parkinson’s disease risk. J Hum Genet 67, 687–690 (2022). https://doi.org/10.1038/s10038-022-01074-5

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