Estimating the mutational load for cardiovascular diseases in Pakistani population

The deleterious genetic variants contributing to certain diseases may differ in terms of number and allele frequency from population to population depending on their evolutionary background. Here, we prioritize the deleterious variants from Pakistani population in manually curated gene list already...

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Bibliographic Details
Published in:	PloS one 2018-02, Vol.13 (2), p.e0192446-e0192446
Main Authors:	Shakeel, Muhammad, Irfan, Muhammad, Khan, Ishtiaq Ahmad
Format:	Article
Language:	eng
Subjects:	Base sequence Biology and Life Sciences Cardiovascular diseases Cardiovascular Diseases - epidemiology Cardiovascular Diseases - genetics Care and treatment Databases, Genetic Gene Frequency Genetic aspects Health aspects Humans Medicine and Health Sciences Mutation Nucleotide sequence Pakistan - epidemiology Pakistanis Risk factors
Online Access:	Get full text
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Summary:	The deleterious genetic variants contributing to certain diseases may differ in terms of number and allele frequency from population to population depending on their evolutionary background. Here, we prioritize the deleterious variants from Pakistani population in manually curated gene list already reported to be associated with common, Mendelian, and congenital cardiovascular diseases (CVDs) using the genome/exome sequencing data of Pakistani individuals publically available in 1000 Genomes Project (PJL), and Exome Aggregation Consortium (ExAC) South Asia. By applying a set of tools such as Combined Annotation Dependent Depletion (CADD), ANNOVAR, and Variant Effect Predictor (VEP), we highlighted 561 potentially detrimental variants from PJL data, and 7374 variants from ExAC South Asian data. Likewise, filtration from ClinVar for CVDs revealed 03 pathogenic and 02 likely pathogenic variants from PJL and 112 pathogenic and 42 likely pathogenic variants from ExAC South Asians. The comparison of derived allele frequencies (DAF) revealed many of these prioritized variants having two fold and higher DAF in Pakistani individuals than in other populations. The highest number of deleterious variants contributing to common CVDs in descending order includes hypertension, atherosclerosis, heart failure, aneurysm, and coronary heart disease, and for Mendelian and congenital CVDs cardiomyopathies, cardiac arrhythmias, and atrioventricular septal defects.
ISSN:	1932-6203 1932-6203