全基因组关联研究的荟萃分析确定了循环总 tau 水平的特定种族相关关联。
Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels.
机构信息
Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
出版信息
Commun Biol. 2022 Apr 8;5(1):336. doi: 10.1038/s42003-022-03287-y.
Circulating total-tau levels can be used as an endophenotype to identify genetic risk factors for tauopathies and related neurological disorders. Here, we confirmed and better characterized the association of the 17q21 MAPT locus with circulating total-tau in 14,721 European participants and identified three novel loci in 953 African American participants (4q31, 5p13, and 6q25) at P < 5 × 10. We additionally detected 14 novel loci at P < 5 × 10, specific to either Europeans or African Americans. Using whole-exome sequence data in 2,279 European participants, we identified ten genes associated with circulating total-tau when aggregating rare variants. Our genetic study sheds light on genes reported to be associated with neurological diseases including stroke, Alzheimer's, and Parkinson's (F5, MAP1B, and BCAS3), with Alzheimer's pathological hallmarks (ADAMTS12, IL15, and FHIT), or with an important function in the brain (PARD3, ELFN2, UBASH3B, SLIT3, and NSD3), and suggests that the genetic architecture of circulating total-tau may differ according to ancestry.
循环总 tau 水平可用作鉴定 tau 病和相关神经障碍的遗传风险因素的内表型。在这里，我们在 14721 名欧洲参与者中证实并更好地描述了 17q21 MAPT 基因座与循环总 tau 之间的关联，并在 953 名非裔美国参与者中鉴定了三个新的基因座（4q31、5p13 和 6q25），其 P 值均小于 5×10。我们还在 P 值小于 5×10 的欧洲人和非裔美国人中分别检测到 14 个新的基因座。使用 2279 名欧洲参与者的全外显子组序列数据，当聚合稀有变异时，我们鉴定出与循环总 tau 相关的 10 个基因。我们的遗传研究揭示了与包括中风、阿尔茨海默病和帕金森病在内的神经疾病相关的基因（F5、MAP1B 和 BCAS3），以及与阿尔茨海默病病理特征相关的基因（ADAMTS12、IL15 和 FHIT），或与大脑重要功能相关的基因（PARD3、ELFN2、UBASH3B、SLIT3 和 NSD3），表明循环总 tau 的遗传结构可能因祖源而异。
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