Clinical translation of hidradenitis suppurativa genetic studies requires global collaboration.
Clinical translation of hidradenitis suppurativa genetic studies requires global collaboration.
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Hidradenitis purativa遗传研究的临床翻译需要全球合作。
DOI：
10.1111/bjd.20749
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Petukhova L
中科院分区：
文献类型：
--
作者：
Jabbour AJ;van Straalen KR;Colvin A;Prens EP;Petukhova L
编辑：化脓性汗管炎(HS)是一种常见的皮肤病，由毛囊，尤其是腋窝、腹股沟和臀部的病理性炎症引起。疾病管理很困难，还有许多未得到满足的医疗需求。有高度的临床异质性。HS可能仅限于某些个体的典型皮肤损害，而对于另一些人，它表现为一种多器官或全身受累的疾病。肿瘤坏死因子抑制是唯一有坚实证据的HS的治疗措施，它未能在高达30%的患者中引起任何临床反应。病原学的异质性被认为是临床表现和治疗反应不同的基础。精准医学的前提是，有相同诊断的人可能有不同的生物病因，需要不同的治疗干预措施。人类基因研究在精密医学中发挥着关键作用，因为它们解决了病因学的异质性，确定了能够区分疾病亚型并能够进行治疗调节的途径。的确，人类基因研究对许多临床领域的医学实践产生了深远的影响，1并且在药物开发中发挥着越来越重要的作用。2例如，检测BRCA1/2基因中的致病变异为改善癌症相关结果的治疗提供了机会，同时也识别了高危家庭成员，以便能够预防性地实施癌症风险管理战略。3对罕见外显子组突变的研究和对非编码多态的全基因组关联研究都促进了这些进展。4尽管HS的遗传力估计为77%，5其遗传结构在很大程度上仍未解决。因此，在不同的人群中进行强有力的基因研究将创造机会，改善对HS患者的护理。过去30年对多因素疾病进行的人类基因研究中出现的指南可以被用来加快HS人类基因研究的临床翻译(表1)。Robust推断从建立足够大的队列开始，以确保足够的基因发现能力。在外显子组研究中威力减弱，因为个体突变在人群中和在GWA中很少见，因为多基因风险变异的影响大小非常小。在小群体中进行的研究很容易受到错误发现的影响，浪费资源，阻碍科学进步。最终将需要数以万计的案例。4.
DEAR EDITOR, Hidradenitis suppurativa (HS) is a prevalent and debilitating skin disease that arises from pathological inflammation in the hair follicle, particularly those located within the axillae, groin and buttocks. Disease management is difficult and there are many unmet medical needs. There is a high degree of clinical heterogeneity. HS can be limited to the presentation of prototypical skin lesions for some individuals, while for others it presents as a disease with multiorgan or systemic involvement. Tumour necrosis factor inhibition is the only therapeutic intervention for HS with a robust evidence base, and it fails to elicit any clinical response in up to 30% of patients. Aetiological heterogeneity is thought to underlie differences in clinical presentation and treatment response. Precision medicine is based on the premise that people who share a diagnosis can have different biological causes of disease that require different therapeutic interventions. Human genetic studies play a pivotal role in precision medicine because they resolve aetiological heterogeneity, identifying pathways that can distinguish disease subtypes and are capable of being therapeutically modulated. Indeed, human genetic studies have had a profound impact on the practice of medicine across many clinical areas, 1 and are playing an increasingly important role in drug development. 2 For example, detection of a pathogenic variant in a BRCA1/2 gene provides the opportunity for treatments that improve cancer-related outcomes, while also identifying at-risk family members so that cancer risk management strategies can be implemented prophylatically. 3 Studies of rare exome mutations and genome-wide association studies (GWAS) of noncoding polymorphisms have both contributed to these advancements. 4 Although HS heritability is estimated at 77%, 5 its genetic architecture remains largely unresolved. Thus, conducting well-powered genetic studies in diverse populations will create opportunities to improve care for patients with HS. Guidelines that have emerged from human genetic studies conducted for multifactorial diseases over the past 30 years can be leveraged to expedite the clinical translation of HS human genetic studies (Table 1).Robust inference starts by building cohorts of sufficient size to ensure adequate power for gene discovery. Power is attenuated in exome studies because individual mutations are rare in the population and in GWAS because polygenic risk variants have very small effect sizes. Studies conducted in small cohorts are vulnerable to false discoveries, wasting resources and impeding scientific advancement. Tens of thousands of cases will ultimately be needed. 4
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DOI：
10.1038/s41576-020-00305-9
发表时间：
2021-05
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Benton ML;Abraham A;LaBella AL;Abbot P;Rokas A;Capra JA
通讯作者：
Capra JA
影响因子：
64.5
作者：
Denny, Joshua C.;Collins, Francis S.
通讯作者：
Collins, Francis S.
DOI：
10.1056/nejmsr1406261
发表时间：
2015-06-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Rehm HL;Berg JS;Brooks LD;Bustamante CD;Evans JP;Landrum MJ;Ledbetter DH;Maglott DR;Martin CL;Nussbaum RL;Plon SE;Ramos EM;Sherry ST;Watson MS;ClinGen
通讯作者：
ClinGen
影响因子：
30.8
作者：
Szustakowski, Joseph D.;Balasubramanian, Suganthi;Reid, Jeffrey G.
通讯作者：
Reid, Jeffrey G.
DOI：
10.6004/jnccn.2020.0017
发表时间：
2020-04-01
影响因子：
13.4
作者：
Daly, Mary B.;Pilarski, Robert;Darlow, Susan D.
通讯作者：
Darlow, Susan D.