Douma Z, Lautier C, Haydar S, Mahjoub T, Grigorescu F
University of Monastir, Faculty of Pharmacy of Monastir - Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Monastir, Tunisia.
University of Montpellier - Molecular Endocrinology - IURC Montpellier, Paris, France.
Acta Endocrinol (Buchar). 2019 Jul-Sep;15(3):364-371. doi: 10.4183/aeb.2019.364.
Genome Wide Association Studies (GWAS) are excellent opportunities to define culprit genes in complex disorders such as the polycystic ovary syndrome (PCOS). PCOS is a prevalent disorder characterized by anovulation, hyperandrogenism and polycystic ovaries, which benefitted from several GWASs in Asians and Europeans revealing more than 20 potential culprit genes near associated single nucleotide variations (SNV). Translation of these findings into the clinical practice raises difficulties since positive hits are surrogate SNVs linked with causative mutations by linkage disequilibrium (LD). Studies in Mediterranean populations (e.g. Southern Europe and North Africa) raise supplementary problems because of a different LD-pattern, which may disrupt the link with causative mutations. Our experience in MEDIGENE program between Tunisia and France enforces the necessity of genetic anthropology studies before translating GWAS data. Tunisians are a heterogeneous population with ancestral Berbers, European, Arab and Sub-Saharan African components while South Europeans display a high level of genetic diversity, partially explained by gene flow from North Africa. Human diversity studies require sampling from Middle East and North Africa (MENA) region that will help to understand genetic factors in complex diseases.
全基因组关联研究（GWAS）是确定多囊卵巢综合征（PCOS）等复杂疾病中致病基因的绝佳机会。PCOS是一种常见疾病，其特征为无排卵、高雄激素血症和多囊卵巢，亚洲人和欧洲人的多项GWAS研究从中受益，发现了与相关单核苷酸变异（SNV）附近的20多个潜在致病基因。将这些发现应用于临床实践存在困难，因为阳性结果是通过连锁不平衡（LD）与致病突变相关联的替代SNV。由于LD模式不同，地中海人群（如南欧和北非）的研究引发了更多问题，这可能会破坏与致病突变的联系。我们在突尼斯和法国之间的MEDIGENE项目中的经验强化了在翻译GWAS数据之前进行遗传人类学研究的必要性。突尼斯人是一个异质群体，有柏柏尔人、欧洲人、阿拉伯人和撒哈拉以南非洲人的祖先成分，而南欧人表现出高度的遗传多样性，部分原因是来自北非的基因流动。人类多样性研究需要从中东和北非（MENA）地区进行抽样，这将有助于了解复杂疾病中的遗传因素。
