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帕金森病的种族和性别特异性全基因组关联研究。

Ethnicity- and sex-specific genome wide association study on Parkinson's disease.

作者信息

Park Kye Won, Ryu Ho-Sung, Shin Eunsoon, Park YoonGi, Jeon Sang Ryong, Kim Seong Yoon, Kim Jae Seung, Koh Seong-Beom, Chung Sun Ju

机构信息

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Pacific Parkinson's Research Centre, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada.

出版信息

NPJ Parkinsons Dis. 2023 Oct 7;9(1):141. doi: 10.1038/s41531-023-00580-3.

Abstract

Most previous genome-wide association studies (GWASs) on Parkinson's disease (PD) focus on the European population. There are several sex-specific clinical differences in PD, but little is known about its genetic background. We aimed to perform an ethnicity-specific and sex-specific GWAS on PD in the Korean population. A total of 1050 PD patients and 5000 controls were included. For primary analysis, we performed a GWAS using a logistic additive model adjusted for age and sex. The same statistical models were applied to sex-specific analyses. Genotyping was performed using a customized microarray chip optimized for the Korean population. Nine single nucleotide polymorphisms (SNPs) including four in the SNCA locus and three from the PARK16 locus were associated with PD in Koreans. The rs34778348 in the LRRK2 locus showed a strong association, though failed to pass cluster quality control. There were no notable genome-wide significant markers near the MAPT or GBA1 loci. In the female-only analysis, rs34778348 in LRRK2 and the four other SNPs in the SNCA showed a strong association with PD. In the male-only analysis, no SNP surpassed the genome-wide significance threshold under Bonferroni correction; however, the most significant signal was rs708726 in the PARK16 locus. This ethnicity- and sex-specific GWAS on PD implicate the pan-ethnic effect of SNCA, the universal but East-Asian inclined effect of PARK16, the East Asian-specific role of LRRK2 G2385R variants, and the possible disproportionate effect of SNCA and PARK16 between sexes for PD susceptibility. These findings suggest the different genetic contributions to sporadic PD in terms of ethnicity and sex.

摘要

以往大多数关于帕金森病(PD)的全基因组关联研究(GWAS)都集中在欧洲人群。PD存在一些性别特异性的临床差异,但其遗传背景却知之甚少。我们旨在对韩国人群中的PD进行种族特异性和性别特异性的GWAS。共纳入了1050例PD患者和5000名对照。对于初步分析,我们使用了针对年龄和性别进行调整的逻辑加性模型进行GWAS。相同的统计模型应用于性别特异性分析。使用针对韩国人群优化的定制微阵列芯片进行基因分型。包括SNCA基因座中的4个和PARK16基因座中的3个在内的9个单核苷酸多态性(SNP)与韩国人的PD相关。LRRK2基因座中的rs34778348显示出很强的关联性,尽管未能通过聚类质量控制。在MAPT或GBA1基因座附近没有显著的全基因组显著标记。在仅针对女性的分析中,LRRK2中的rs34778348和SNCA中的其他4个SNP与PD显示出很强的关联性。在仅针对男性的分析中,在Bonferroni校正下没有SNP超过全基因组显著性阈值;然而,最显著的信号是PARK16基因座中的rs708726。这项针对PD的种族和性别特异性GWAS表明,SNCA具有泛种族效应,PARK16具有普遍但东亚倾向的效应,LRRK2 G2385R变体具有东亚特异性作用,以及SNCA和PARK16在性别之间对PD易感性可能存在不成比例的影响。这些发现表明,在种族和性别方面,散发性PD存在不同的遗传贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2a2/10560250/05cd1de1b144/41531_2023_580_Fig1_HTML.jpg

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