Download Highly replicable GWAS findings on endophenotypes of

Taiwan Young-Onset Hypertension Genomics Study: splitting or merging
Wen-Harn Pan, PhD
Division of Preventive Medicine and Health Services Research, Institute of
Population Health Sciences, National Health Research Institutes
Institute of Biomedical Sciences, Academia Sinica
Hypertension is a common and complex disorder with great public health impact.
Identifying genetic variants will contribute to understanding of hypertension genetics,
efficacy of genetic screening and management of hypertension. Although many
large-scale genome-wide association studies applying the state-of-art genotyping
platforms have been performed and produced massive amount of genetic information,
very few studies have successfully identified replicable large-impact hypertension loci,
not to mention the scanty Asian studies.
We proposed to splitting the phenotype, but merging the genetic information with
biological considerations. Gene mapping for endophenotypes of hypertension such as
adiponectin and angiotensin converting enzyme activity has been very successful and
highly replicable. Variants of CDH13 predict adiponectin concentration in the blood,
which is associated with cardiometabolic diseases. ABO and ACE variants jointly
predict ACE activity and blood pressure response to ACEI. By applying gene-based or
region-based Genome-wide association approach to two large series of YOH studies
(a family-based and a case-control study), we have identified four genes (IGF1,
SLC4A4, WWOX, and SFMBT1) which are replicated by the Hong Kong
Hypertension Study. We are also able to show that gene expression levels of these
genes are associated with disease related SNPs.
Genomics convergence method is promising in unraveling the hypertension etiology.
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