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Background <p>Parkinson’s disease (PD) is a genetically heterogeneous neurodegenerative disorder. While monogenic forms are well-characterized, the diagnostic utility of next-generation sequencing (NGS) in PD remains unclear. This meta-analysis aimed to evaluate the diagnostic yield of NGS technologies, including whole exome sequencing (WES), targeted gene panels (TGP), and multiplex ligation-dependent probe amplification (MLPA), in identifying pathogenic/likely pathogenic (P/LP) variants in PD and to explore global disparities in access to genetic testing.</p> Methods <p>A systematic search was conducted across PubMed, Scopus, and Google Scholar using relevant MeSH terms and keywords. Studies published in English up to April 2024 were considered. Clinical studies using NGS or MLPA to assess genetic variants in PD patients were included. Data was extracted from 13 eligible studies involving 4,712 individuals with familial, sporadic, early-onset parkinson’s disease (EOPD), or late-onset parkinson’s disease (LOPD). Quality assessment was performed using the Newcastle–Ottawa Scale (NOS). Random-effects meta-analysis was applied to estimate diagnostic yields, assess heterogeneity (I²), and evaluate publication bias using Egger’s test.</p> Results <p>The overall diagnostic yield was 12% (95% confidence interval (CI, 0.07–0.19). Yields varied by genomic technology: 21% for WES, 9% for TGP, and 5% for MLPA. Familial PD had a higher diagnostic yield (19%) than sporadic PD (5%), and EOPD showed higher yield (13%) compared to LOPD (11%). Frequently detected pathogenic/likely pathogenic variants occurred in <i>GBA</i> (39%), <i>PRKN</i> (28%), and <i>LRRK2</i> (16%) genes. Notable heterogeneity was observed across studies (I² = 97.9%). Global analysis showed unequal access to genetic testing, with higher adoption in high inequality-adjusted human development index (IHDI) countries.</p> Conclusions <p>Genomic technologies, especially WES, provide meaningful diagnostic insights in PD, particularly in familial and early-onset cases. However, significant disparities exist in global adoption, highlighting a need for broader access and standardized protocols. These findings underscore the importance of integrating genetic screening into routine clinical practice and expanding research efforts in underrepresented populations to advance precision medicine in PD.</p>

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Clinical genetic testing in Parkinson’s disease: meta-analysis of diagnostic yield across sequencing technologies and global regions

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月16日

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  • Anitha Saminathan,
  • Indhumathi Nagarthinam,
  • Vijayashankar Paramanandam,
  • Vettriselvi Venkatesan,
  • Teena Koshy

摘要

Background

Parkinson’s disease (PD) is a genetically heterogeneous neurodegenerative disorder. While monogenic forms are well-characterized, the diagnostic utility of next-generation sequencing (NGS) in PD remains unclear. This meta-analysis aimed to evaluate the diagnostic yield of NGS technologies, including whole exome sequencing (WES), targeted gene panels (TGP), and multiplex ligation-dependent probe amplification (MLPA), in identifying pathogenic/likely pathogenic (P/LP) variants in PD and to explore global disparities in access to genetic testing.

Methods

A systematic search was conducted across PubMed, Scopus, and Google Scholar using relevant MeSH terms and keywords. Studies published in English up to April 2024 were considered. Clinical studies using NGS or MLPA to assess genetic variants in PD patients were included. Data was extracted from 13 eligible studies involving 4,712 individuals with familial, sporadic, early-onset parkinson’s disease (EOPD), or late-onset parkinson’s disease (LOPD). Quality assessment was performed using the Newcastle–Ottawa Scale (NOS). Random-effects meta-analysis was applied to estimate diagnostic yields, assess heterogeneity (I²), and evaluate publication bias using Egger’s test.

Results

The overall diagnostic yield was 12% (95% confidence interval (CI, 0.07–0.19). Yields varied by genomic technology: 21% for WES, 9% for TGP, and 5% for MLPA. Familial PD had a higher diagnostic yield (19%) than sporadic PD (5%), and EOPD showed higher yield (13%) compared to LOPD (11%). Frequently detected pathogenic/likely pathogenic variants occurred in GBA (39%), PRKN (28%), and LRRK2 (16%) genes. Notable heterogeneity was observed across studies (I² = 97.9%). Global analysis showed unequal access to genetic testing, with higher adoption in high inequality-adjusted human development index (IHDI) countries.

Conclusions

Genomic technologies, especially WES, provide meaningful diagnostic insights in PD, particularly in familial and early-onset cases. However, significant disparities exist in global adoption, highlighting a need for broader access and standardized protocols. These findings underscore the importance of integrating genetic screening into routine clinical practice and expanding research efforts in underrepresented populations to advance precision medicine in PD.