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.

对于患者的健康，脱发可能会使人衰弱，大多数脱发障碍既不理解且良好。这项研究正在调查自身免疫，疤痕和非囊脱发的脱发： - 额叶纤维性脱发（FFA），这是一种日益普遍的疤痕和炎症自身免疫性，几乎完全影响女性。 - 雌激素（AGA），这是由于激素和遗传学引起的，通常会影响男性和女性。在FFA中，皮肤炎症始于头皮，这受到严重燃烧和瘙痒的影响。炎症非常困难，疾病将努力影响整个头皮，尤其是如果不接受抑制一个人的免疫系统的强药物治疗。患有这种疾病的妇女通常在心理上非常痛苦。总体上，FFA的治疗方法不足，在我们最初的大规模研究之前，对疾病引起的疾病的了解很少，我们的团队发现了许多与FFA密切相关的基因。在AA中，较深的皮肤层有炎症，在皮肤表面上并不明显。这种情况通常会导致脱发的斑块，通常会扩大和结合，从而导致头皮，眉毛或通用头皮以及身体脱落。应力是AA的常见归因因素，已知会触发和加剧条件。关于基于AA的遗传机制的知识，从分子角度来看，在许多方面，该机制也被认为与FFA相似。人们认为，激素在AA和FFA.AGA的发病机理中起作用，在男性和女性中也很常见，而且在青少年中也很常见。广泛认为是遗传和荷尔蒙原因，这种情况可能会出现女性和男性秃发的变薄和头发缘衰退。 AGA经常与AA和FFA共存，并且有越来越多的证据表明激素因素在两者中都起作用。拟议的项目将在多疾病分析中使用现代统计遗传方法，以尝试解决这些形式的脱发形式如何在遗传上相关。为了最大程度地提高这种方法的能力，我们还将评估具有大规模遗传关联研究的相关条件的遗传途径共享，包括全身性红斑狼疮（SLE）。拟议的项目有望提高统计能力，以发现发现新的遗传关联的统计能力，可以改善我们发展这些疾病的能力，还可以帮助我们确定这些疾病的能力，并确定这些疾病的能力，并确定了不同的疾病。后者有可能告知每种最合适的治疗策略，这可以通过重新使用现有药物或发现新药物。我们的研究人员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（Michael Simpson）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，并指导我们发展更好的治疗方法，而脱发的患者非常需要这种治疗方法。