Common disease-associated gene variants in a Saudi Arabian population

Abstract

BACKGROUND: Screening programs for the most prevalent conditions occurring in a country is an evidence-based prevention strategy. The burden of autosomal recessive disease variations in Saudi Arabia is high because of the highly consanguineous population. The optimal solution for estimating the carrier frequency of the most prevalent diseases is carrier screening. OBJECTIVES: Identify the most influential recessive alleles associated with disease in the Saudi population. DESIGN: We used clinical whole-exome sequencing data from an in-house familial database to evaluate the most prevalent genetic variations associated with disease in a Saudi population. SETTINGS: King Abdullah International Medical Research Center (KAIMRC) and King Abdulaziz Medical City. METHODS: Whole exome sequencing data obtained from clinical studies of family members, a cohort of 1314 affected and unaffected individuals, were filtered using the in-house pipeline to extract the most prevalent variant in the dataset. MAIN OUTCOME MEASURES: Most prevalent genetic variations associated with disease in the Saudi population. SAMPLE SIZE: 1314 affected and unaffected individuals. RESULTS: We identified 37 autosomal recessive variants and two heterozygous X-linked variants in 35 genes associated with the most prevalent disorders, which included hematologic (32%), endocrine (21%), metabolic (11%) and immunological (10%) diseases. CONCLUSION: This study provides an update of the most frequently occurring alleles, which support future carrier screening programs. LIMITATIONS: Single center that might represent the different regions but may be biased. In addition, most of the families included in the database are part of the proband's genetic identification for specific phenotypes. CONFLICT OF INTEREST: None.

Carrier frequency estimation of pathogenic variants of autosomal recessive and X-linked recessive mendelian disorders using exome sequencing data in 1,642 Thais

“…Our assertions are substantiated by evidence gleaned from our analysis of inheritance patterns among patients referred for genetic testing at our institution. Notably, our findings reveal that only 25% of positive tests exhibit inheritance in an autosomal recessive pattern, in stark contrast to Middle Eastern countries where the autosomal recessive pattern can reach up to 80%, particularly in regions where consanguinity is commonplace [ 25 ]. It is imperative to underscore that thalassemia and hemoglobinopathies are highly prevalent in our region, and the pseudoautosomal dominant pattern observed in our study is reflective of this prevalence rather than indicative of prevailing marriage patterns.…”

Familial Screening for the Prevention of Rare Diseases: A Focus on Lipodystrophy in Southern Saudi Arabia

“…Notably, 80% of RDs are inherited, and 63% appear in early childhood [ 23 ]. In Saudi Arabia, the prevalence of RDs, especially autosomal recessive disorders, is higher due to the high frequency of consanguineous marriages, which increase the chance of offspring inheriting two copies of pathogenic alleles [ 1 , 8 ].…”

Prevalence of Consanguineous Marriage among Saudi Citizens of Albaha, a Cross-Sectional Study

“…Evidence for the association between the incidence of hereditary diseases and CM is well-established. CM has been found to be related to increased risks of haemoglobinopathies, intellectual disabilities, congenital glaucoma, ciliopathies, disorders related to inborn errors of metabolism, retinal dystrophies, hearing loss, primary microcephaly, and familial hypercholesterolaemia [ 24 , 25 , 26 , 27 ]. Such health issues and diseases resulting from CM can negatively impact the economy and the healthcare system [ 15 , 28 ].…”