Shared and distinct genetic architecture of autoimmune and hormonal alopecias

脱发可能会使患者非常虚弱，大多数脱发障碍既没有得到很好的理解，也没有得到很好的治疗。这项研究正在研究自身免疫、疤痕和非疤痕脱发：-额部纤维性脱发(FFA)，一种越来越常见的疤痕和炎症性自身免疫性疾病，几乎只影响女性。-斑秃(AA)，这是人类最常见的自身免疫性疾病，是一种影响男性、女性和儿童的非疤痕形式的脱发；以及-雄激素脱发(AGA)，这是由激素和遗传学引起的，通常影响男性和女性。在FFA中，皮肤炎症始于头皮，受到强烈灼热和瘙痒的影响。这种炎症很难控制，这种疾病会向前发展，影响整个头皮，特别是如果不用抑制免疫系统的强效药物治疗的话。患有这种疾病的女性通常在心理上非常痛苦。总的来说，对FFA的治疗是不够的，在我们最初的大规模研究之前，人们对这种疾病的病因知之甚少，我们的团队在研究中发现了一些与FFA密切相关的基因。在再生障碍性贫血中，皮肤深层有炎症，皮肤表面不明显。这种情况通常会导致片状脱发，这些脱发通常会扩大并结合，导致完整的头皮、眉毛或全身头皮和身体脱发。压力是再生障碍性贫血的一个常见的归因因素，众所周知，它会引发和加剧这种情况。人们对AA的遗传机制有很多了解，从分子上讲，AA在许多方面也被认为与FFA相似。激素被认为在AA和FFA的发病机制中发挥了作用。AGA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荷尔蒙的原因，这种情况可能会出现稀疏和头发边缘后退的女性和男性模式秃顶。AGA经常与AA和FFA共存，越来越多的证据表明激素因素在这两种疾病中都起到了作用。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基因上相互关联。为了最大限度地发挥这一方法的能力，我们还将评估遗传途径与相关疾病(包括系统性红斑狼疮(SLE))的共享情况。拟议的项目承诺提高发现新遗传关联的统计能力，提高我们预测这些疾病风险的能力，同时也有助于我们识别共同和独特的易感生物学途径。后者有可能为每种药物提供最合适的治疗策略，这可能是通过重新调整现有药物的用途或发现新的药物。我们的研究团队设在伦敦国王学院，这项研究的学术合作伙伴是迈克尔·辛普森教授。我们坚信，这项研究将加强我们对几种基本疾病过程的了解，并指导我们开发更好的治疗方法，这是脱发患者非常需要的。

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.