Research Center of the Sainte-Justine University Hospital, University of Montreal, QC, Canada.
Departments of Pediatrics, Biochemistry and Molecular Medicine, University of Montreal, QC, Canada.
Adv Exp Med Biol. 2022;1390:327-342. doi: 10.1007/978-3-031-11836-4_19.
While genome-wide association studies (GWAS) on levels of nuclear receptors are sparse, the genetics of ligands of these receptors (steroid hormones, thyroid hormones, and liposoluble vitamins) have been extensively studied in GWAS of predominantly European populations. Hundreds of genetic variants across the genome have been associated with serum levels of nuclear receptor ligands, shedding light on the physiology of hormone metabolism. These GWAS findings have been used to explore causal associations of these hormones with complex human traits and diseases in Mendelian randomization (MR) studies, and in studies using polygenic risk scores to quantify the genetic predisposition to higher/lower hormone levels. As such, besides providing insights into hormonal pathophysiology and its causal relationship with clinical complications, GWAS-identified genetic markers could ultimately play an important role in the daily clinical management of patients. As large trans-ethnic GWAS on levels of nuclear receptor ligands emerge, and with the fast advances in genotyping techniques and constant decrease of the genotyping costs, studying an individual's genetically predicted hormonal profile could be the next step in personalizing the management of patients with pathologies related to nuclear receptors and their ligands.
虽然核受体水平的全基因组关联研究（GWAS）很少，但这些受体的配体（甾体激素、甲状腺激素和脂溶性维生素）的遗传学在主要为欧洲人群的 GWAS 中得到了广泛研究。数百个基因组范围内的遗传变异与核受体配体的血清水平相关，揭示了激素代谢的生理学。这些 GWAS 发现已被用于探索这些激素与复杂人类特征和疾病的因果关系，在孟德尔随机化（MR）研究中，以及在使用多基因风险评分来量化更高/更低激素水平的遗传易感性的研究中。因此，除了提供对激素病理生理学及其与临床并发症的因果关系的深入了解外，GWAS 确定的遗传标记最终可能在患者的日常临床管理中发挥重要作用。随着核受体配体水平的大型跨种族 GWAS 的出现，以及基因分型技术的快速进步和基因分型成本的不断降低，研究个体的遗传预测激素谱可能是个性化管理与核受体及其配体相关的病理患者的下一步。
