L-001 A THREE-STAGE GENOME-WIDE ASSOCIATION STUDY OF YANG-ONSET HYPERTENSION IN HAN CHINESE POPULATION OF TAIWAN

Abstract

Listen

Translate article

Background Hypertension is a common and complex disorder. To identify its susceptibility genes may contribute to genetic screening and treatment for hypertension. Although many large-scale genome-wide association studies have been performed, only a few studies have successfully identified the loci that are related to the hypertension, not to mention the scanty Asian studies. Young-onset hypertension (YOH) may be a more feasible target disorder to investigate than the late-onset one due to its stronger genetic component. Methods We performed a three-stage genome-wide association study to map YOH susceptibility genes. In the first stage, we analyzed 400 YOH cases and 400 age and gender matched controls with BMI adjusted in all the analyses. In the second stage, an independent sample (600 YOH cases and 600 age and gender matched controls) was used to verify the results. Besides the conventional single locus test, Multilocus association tests and pair were used to increase the power to identify potential SNPs. After considering stringent adjustments of multiple testing, 14 SNP septets from the multilocus test and 20 SNP pairs from the epistasis test were selected to verify. In the third stage, gene expression profiles of the genes located in these regions were also tested to further confirm those finding. Results Finally, three genes (GSN, LARS and ACTN4) from the multilocus test and one gene pair (LIPC and CELF5) were verified successfully. Some animal experiments also showed that GSN is involved in the inflammatory processes, which is an important participant in the pathophysiology of hypertension. LIPC plays a major role in the regulation of plasma lipids and is involved in the glycerolipid metabolism. Those genes are novel hypertension targets identified in this YOH GWA study of the Han Chinese population.