Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD.
Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD.
Ann Neurol. 2021 Jul;90(1):35-42. doi: 10.1002/ana.26090. Epub 2021 May 24.
Parkinson's disease (PD) is a complex neurodegenerative disorder. Men are on average ~ 1.5 times more likely to develop PD compared to women with European ancestry. Over the years, genomewide association studies (GWAS) have identified numerous genetic risk factors for PD, however, it is unclear whether genetics contribute to disease etiology in a sex-specific manner.
In an effort to study sex-specific genetic factors associated with PD, we explored 2 large genetic datasets from the International Parkinson's Disease Genomics Consortium and the UK Biobank consisting of 13,020 male PD cases, 7,936 paternal proxy cases, 89,660 male controls, 7,947 female PD cases, 5,473 maternal proxy cases, and 90,662 female controls. We performed GWAS meta-analyses to identify distinct patterns of genetic risk contributing to disease in male versus female PD cases.
In total, 19 genomewide significant regions were identified and no sex-specific effects were observed. A high genetic correlation between the male and female PD GWAS were identified (rg = 0.877) and heritability estimates were identical between male and female PD cases (~ 20%).
We did not detect any significant genetic differences between male or female PD cases. Our study does not support the notion that common genetic variation on the autosomes could explain the difference in prevalence of PD between males and females cases at least when considering the current sample size under study. Further studies are warranted to investigate the genetic architecture of PD explained by X and Y chromosomes and further evaluate environmental effects that could potentially contribute to PD etiology in male versus female patients. ANN NEUROL 2021;90:41-48.
帕金森病（PD）是一种复杂的神经退行性疾病。与具有欧洲血统的女性相比，男性平均患 PD 的可能性高 1.5 倍左右。多年来，全基因组关联研究（GWAS）已经确定了许多 PD 的遗传风险因素，但尚不清楚遗传因素是否以性别特异性的方式导致疾病的病因。
为了研究与 PD 相关的性别特异性遗传因素，我们探索了来自国际帕金森病基因组学联合会和英国生物银行的 2 个大型遗传数据集，其中包含 13020 名男性 PD 病例、7936 名父亲代理病例、89660 名男性对照、7947 名女性 PD 病例、5473 名母亲代理病例和 90662 名女性对照。我们进行了 GWAS 荟萃分析，以确定导致男性和女性 PD 病例疾病的不同遗传风险模式。
总共确定了 19 个全基因组显著区域，没有观察到性别特异性影响。男性和女性 PD GWAS 之间存在高度遗传相关性（rg=0.877），男性和女性 PD 病例的遗传率估计值相同（约 20%）。
我们没有在男性或女性 PD 病例之间检测到任何显著的遗传差异。我们的研究不支持这样一种观点，即常染色体上的常见遗传变异可以解释男性和女性 PD 病例之间患病率的差异，至少在考虑当前研究样本量的情况下是如此。需要进一步的研究来调查 X 和 Y 染色体解释 PD 遗传结构的情况，并进一步评估可能导致男性和女性患者 PD 病因的环境影响。ANN NEUROL 2021;90:41-48。
