Scholarlink

<p><i>LRRK2</i> variants are key genetic risk factors for Parkinson’s Disease (PD). We conducted a per-domain rare coding variant burden analysis, including 8,888 PD cases and 69,412 controls. In meta-analysis, the Kinase domain was strongly associated with PD (Exonic: <i>P</i><sup><i>FDR</i></sup> = 1.61 × 10<sup>−22</sup>, Non-synonymous: <i>P</i><sup><i>FDR</i></sup> = 1.54 × 10<sup>−23</sup>, CADD &gt; 20: <i>P</i><sup><i>FDR</i></sup> = 3.09 × 10<sup>−24</sup>). Excluding the p.G2019S variant nullified this effect. Nominal associations were found in the ANK and Roc-COR domains, with potentially protective variants, p.R793M and p.Q1353K.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

LRRK2 rare-variant per-domain genetic burden in Parkinson’s Disease: association confined to the kinase domain

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月29日

查看全文
  • Sitki Cem Parlar,
  • Konstantin Senkevich,
  • Eric Yu,
  • Jennifer A. Ruskey,
  • Jamil Ahmad,
  • Farnaz Asayesh,
  • Dan Spiegelman,
  • Cheryl Waters,
  • Oury Monchi,
  • Yves Dauvilliers,
  • Nicolas Dupré,
  • Lior Greenbaum,
  • Sharon Hassin-Baer,
  • Irina Miliukhina,
  • Alla Timofeeva,
  • Anton Emelyanov,
  • Sofya Pchelina,
  • Roy N. Alcalay,
  • Edward A. Fon,
  • Jean-François Trempe,
  • Ziv Gan-Or

摘要

LRRK2 variants are key genetic risk factors for Parkinson’s Disease (PD). We conducted a per-domain rare coding variant burden analysis, including 8,888 PD cases and 69,412 controls. In meta-analysis, the Kinase domain was strongly associated with PD (Exonic: PFDR = 1.61 × 10−22, Non-synonymous: PFDR = 1.54 × 10−23, CADD > 20: PFDR = 3.09 × 10−24). Excluding the p.G2019S variant nullified this effect. Nominal associations were found in the ANK and Roc-COR domains, with potentially protective variants, p.R793M and p.Q1353K.