Shared and distinct genetic architecture of autoimmune and hormonal alopecias

自身免疫性脱发和激素性脱发的共同和独特的遗传结构

• 批准号: MR/X030466/1
• 负责人: Christos Tziotzios
• 金额: $ 27.48万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX030466%2F1
• 关键词: Shared; distinct; genetic; architecture; autoimmune

Hair loss can be very debilitating for patient wellbeing and most hair loss disorders are neither well understood, nor well-treated. This research study is investigating autoimmune, scarring and non-scarring hair loss: - frontal fibrosing alopecia (FFA), an increasingly common scarring and inflammatory autoimmune condition affecting almost exclusively women.- alopecia areata (AA), which is the commonest human autoimmune disease and a non-scarring form of hair loss affecting men, women and children; and- androgenetic alopecia (AGA), which is due to hormones and genetics and commonly affects men and women.In FFA, skin inflammation starts from the scalp, which is affected by intense burning and itching. The inflammation is very difficult to manage and the disease will forge ahead to affect the entire scalp, especially if not treated with strong drugs that suppress one's immune system. Women suffering from this condition are usually very distressed psychologically. Treatments for FFA on the whole are inadequate and very little was known about what causes the disease, prior to our original large-scale research study, where our team has discovered a number of genes that are strongly associated with FFA. In AA, there is inflammation in deeper skin layers, which is not evident on the skin surface. The condition commonly causes patches of hair loss, which can often enlarge and coalesce, leading to complete scalp, eyebrow or universal scalp and body hair loss. Stress is a common attributing factor of AA, which is known to trigger and exacerbate the condition. A lot is known about the genetic mechanisms underpinning AA, which, in molecular terms, is also thought to be similar in many respects to FFA. Hormones are thought to play a role in the pathogenesis of both AA and FFA.AGA is very common in men and women but also in adolescents. Widely thought of as of genetic and hormonal cause, the condition may present with thinning and hair margin recession in female and male pattern baldness. AGA often co-exists with AA and FFA and there is increasing evidence that hormonal factors play a role in both. The proposed project will use modern statistical genetic approaches in a multi-disease analysis to try and resolve how these forms of alopecia correlate genetically. To maximise the ability of this approach, we will also evaluate sharing of genetic pathways with related conditions for which large scale genetic association studies are available, including systemic lupus erythematosus (SLE).The proposed project promises to improve statistical power for the discovery of new genetic associations, improve our ability to predict risk of developing these diseases whilst also helpings us identify shared and distinct biological pathways of susceptibility. The latter has the potential to inform about the most suited treatment strategy for each, which could be by either repurposing existing drugs or discovering new ones.Our team of researchers is based at King's College London and the academic partner in this research is Prof Michael Simpson. We strongly believe that this research study will enhance our understanding of several basic disease processes and direct us towards developing better treatments, which alopecia sufferers are in so desparate need for.

脱发对患者的健康非常不利，大多数脱发疾病既没有得到很好的理解，也没有得到很好的治疗。这项研究正在调查自身免疫性，瘢痕性和非瘢痕性脱发：-额叶纤维性脱发（FFA），一种越来越常见的瘢痕和炎症性自身免疫性疾病，几乎只影响女性。斑秃（AA），这是最常见的人类自身免疫性疾病，也是一种影响男性、女性和儿童的无疤痕脱发形式;以及-雄激素性脱发（阿加），这是由于激素和遗传引起的，通常影响男性和女性。这种炎症很难控制，疾病会继续影响整个头皮，特别是如果不使用抑制免疫系统的强效药物治疗。患有这种疾病的妇女通常在心理上非常痛苦。总的来说，FFA的治疗是不够的，在我们最初的大规模研究之前，我们对这种疾病的病因知之甚少，我们的团队发现了一些与FFA密切相关的基因。在AA中，皮肤深层有炎症，这在皮肤表面上不明显。这种情况通常会导致脱发的斑块，这些斑块通常会扩大和合并，导致完全的头皮，眉毛或普遍的头皮和身体脱发。压力是AA的常见归因因素，已知其触发并加重病情。关于AA的遗传机制已经知道很多，从分子角度来看，它也被认为在许多方面与FFA相似。激素被认为在AA和FFA的发病机制中起作用。阿加在男性和女性中非常常见，但在青少年中也很常见。被广泛认为是遗传和激素的原因，这种情况可能会出现女性和男性脱发的稀疏和头发边缘衰退。阿加通常与AA和FFA共存，越来越多的证据表明激素因素在两者中起作用。拟议的项目将在多疾病分析中使用现代统计遗传学方法，试图解决这些形式的脱发如何在遗传上相互关联。为了最大限度地提高这种方法的能力，我们还将评估与大规模遗传关联研究相关疾病的遗传途径共享，包括系统性红斑狼疮（SLE）。拟议的项目有望提高发现新遗传关联的统计能力，提高我们预测发展这些疾病的风险的能力，同时也帮助我们识别共同的和不同的易感性生物学途径。后者有可能为每种疾病提供最适合的治疗策略，可以通过重新利用现有药物或发现新药物。我们的研究团队位于伦敦国王学院，这项研究的学术合作伙伴是迈克尔·辛普森教授。我们坚信，这项研究将增强我们对几种基本疾病过程的理解，并指导我们开发更好的治疗方法，这是脱发患者迫切需要的。