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Phenome-wide association study of a comprehensive health check-up database in a Korea population: Clinical application & trans-ethnic comparison

By Eun Kyung Choe, Manu Shivakumar, Anurag Verma, Shefali Setia Verma, Seung Ho Choi, Joo Sung Kim, Dokyoon Kim

Posted 01 Jun 2020
bioRxiv DOI: 10.1101/2020.05.31.126201

Background: The expanding use of the phenome-wide association study (PheWAS) faces challenges in the context of using International Classification of Diseases billing codes for phenotype definition, imbalanced study population ethnicity, and constrained application of the results to clinical practice or research. Methods: We performed a PheWAS utilizing deep phenotypes corroborated by comprehensive health check-ups in a Korean population, along with trans-ethnic comparisons through the UK Biobank and Biobank Japan Project. Network analysis, visualization of cross-phenotype mapping, and causal inference mapping with Mendelian randomization were conducted in order to make robust, clinically applicable interpretations. Results: Of the 136 phenotypes extracted from the health check-up database, the PheWAS associated 65 phenotypes with 14,101 significant variants (P < 4.92x10-10). In the association study for body mass index, our population showed 583 exclusive loci relative to the Japanese population and 669 exclusive loci relative to the European population. In the meta-analysis with Korean and Japanese populations, 72.5% of phenotypes had uniquely significant variants. Tumor markers and hematologic phenotypes had a high degree of phenotype-phenotype pairs. By Mendelian randomization, one skeletal muscle mass phenotype was causal and two were outcomes. Among phenotype pairs from the genotype-driven cross-phenotype associations, 71.65% also demonstrated penetrance in correlation analysis using a clinical database. Conclusions: This comprehensive analysis of PheWAS results based on a health check-up database will provide researchers and clinicians with a panoramic overview of the networks among multiple phenotypes and genetic variants, laying groundwork for the practical application of precision medicine. ### Competing Interest Statement The authors have declared no competing interest.

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