Autoimmune diseases (ADs) are complex diseases influenced by various genetic and environmental factors, often exhibiting familial aggregation and heritability. While genetic contribution to ADs varies, studies have demonstrated a strong link between genetic susceptibility and disease occurrence, especially genes involving in major histocompatibility complex (MHC) and non-MHC loci play major roles. Additionally, sex-biased heritability, particularly linked to X-chromosome, contributes to higher prevalence of ADs in females. While over 300 genetic loci are identified by genome-wide association studies (GWAS) linked to AD risk, a significant portion of heritability still remains unexplained. Epidemiological studies confirm familial clustering of AD due to shared genetic and environmental triggers. Assessing the interplay of genetic screening in familial aggregation can contribute to the knowledge on the genetic architecture of ADs, which is crucial for improving early diagnosis and design personalized medications and treatment.