دانلود رایگان مقاله انگلیسی بررسی مختصر دهه مطالعه همخوانی سراسر ژنوم در فشار خون اولیه - هینداوی 2018

Primary hypertension is widely believed to be a complex polygenic disorder with the manifestation influenced by the interactions of genomic and environmental factors making identification of susceptibility genes a major challenge. With major advancement in high-throughput genotyping technology, genome-wide association study (GWAS) has become a powerful tool for researchers studying genetically complex diseases. GWASs work through revealing links between DNA sequence variation and a disease or trait with biomedical importance. The human genome is a very long DNA sequence which consists of billions of nucleotides arranged in a unique way. A single base-pair change in the DNA sequence is known as a single nucleotide polymorphism (SNP). With the help of modern genotyping techniques such as chip-based genotyping arrays, thousands of SNPs can be genotyped easily. Large-scale GWASs, in which more than half a million of common SNPs are genotyped and analyzed for disease association in hundreds of thousands of cases and controls, have been broadly successful in identifying SNPs associated with heart diseases, diabetes, autoimmune diseases, and psychiatric disorders. It is however still debatable whether GWAS is the best approach for hypertension. The following is a brief overview on the outcomes of a decade of GWASs on primary hypertension.

4. Conclusion

Although some of the SNPs identified by GWAS on primary hypertension associates with similar biological pathways as Mendelian or early-onset forms of hypertension (validating the study approach), none of the SNPs identified had a large size effect (≤1 mmHg) to be of significance to an individual patient. The ultimate goals of performing these GWASs are to determine the genetic factors regulating blood pressure that can be used to make predictions about who is at risk of developing hypertension and to identify the biological pathways of the disease allowing for identification of novel targets for treatment or even prevention strategies. As currently no direct clinical application of these GWAS findings can be made, it is still debatable whether GWAS is the best approach to identify the biological underpinnings of primary hypertension. Even though yet-to-be-discovered Oriental-specific loci or rare SNPs that might have larger effect size may increase the variance for blood pressure that can be explained by genetic variation, information on epigenetic modulation (e.g., DNA methylation, posttranslational modifications of proteins, or even gut microbiota [20, 74–78]) may still be needed to explain the total heritability of raised blood pressure which cannot be captured by GWASs.