Portability of Gwas Results between Ethnic Populations: Genetic Markers for Polycystic Ovary Syndrome (Pcos) in Mediterranean Area

Abstract

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.

Importance of Dehydroepiandrosterone Sulfate Assessment with Special Attention for Adrenal Tumours and Arterial Hypertension

“…Assessment of DHEAS and AT in women is only a clinical start point for much more complex investigations. Genetic markers for polycystic ovary syndrome are studied today even between ethnic populations, as in famous MEDIGENE program (22).…”

How Geneticists Contribute to Understanding of Covid-19 Disease Pathogenicity

“…In this population it was observed a lower incidence of COVID-19 in children and females compared to adults and males. While Iceland may represent an excellent model to understand genetics of COVID-19, the Mediterranean populations are by contrast more complicated since Mediterranean borders were places of admixed populations for millennia, including the admixture with North African populations (27)(28)(29). It is worth saying that analysis of genetic data triggering the MetS and its components from the MEDIGENE program ((https:// cordis.europa.eu/result/rcn/195753_fr.html) in the Mediterranean area would be of crucial importance.…”

The Association of CYP17A1, CYP19A1, and SHBG Gene Polymorphisms in Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-Analysis

“…Single nucleotide polymorphisms (SNPs) might reveal functional changes caused by amino acid variation or gene expression regulation. Candidate gene investigations provide insight into different frequency distributions in healthy and diseased populations ( Douma et al, 2019 ); however, previous studies exploring the potential relationship between PCOS susceptibility and CYP17A1/CYP19A1/SHBG gene polymorphisms used statistically insufficient samples sizes and reported inconsistent findings ( Li et al, 2012 ; Liao and Cao, 2020 ; Li et al, 2021 ; Sharma et al, 2021 ). Thus, The search acronym (PICO) for our meta-analysis to elucidate the relationship between CYP17A1/CYP19A1/SHBG gene polymorphisms in both wild type and mutant type and PCOS susceptibility in general populations in a larger study cohort.…”