关键词: 全基因组测序, 单基因遗传病, 体检, 健康管理

Abstract:

Objective To investigate the benefits of whole-genome sequencing（WGS） in physical examination population. Methods A total of 70 subjects who underwent WGS at Zhongshan Hospital of Fudan University from March 2023 to July 2024 for physical examination were enrolled. The general data were collected，and bioinformatics analysis was performed on the sequencing data. The pathogenicity of the detected mutations was analyzed using the sequence variation interpretation guidelines developed by American College of Medical Genetics and Genomics（ACMG）. Results A total of 390 genetic variations were detected in 70 subjects undergoing physical examination，which included 69 pathogenic variations（17.7%） and 76 suspected pathogenic variations（19.5%）. In 16 cases（22.9%），19 variations that can cause monogenic genetic diseases were detected. Totally，60 cases（85.7%） were detected with at least one pathogenic or suspected pathogenic variation associated with recessive genetic diseases or X-linked genetic diseases. The top 5 genes with high detection rates were GJB2（6.67%），HFE（4.17%），DUOX2（3.33%），SLC26A4（3.33%） and SERPINB7（2.50%）. Among the 70 subjects who underwent physical examination，5（7.14%），2（2.86%），1（1.43%），1（1.43%），1（1.43%） and 1（1.43%） of them were found to be at high genetic risk for Alzheimer's disease，ankylosing spondylitis，Sjogren's syndrome，gallstones，prostate cancer and multiple myeloma，respectively. Another 2 subjects（2.86%） and 1 subject（1.43%） were found to have low genetic risk for psoriasis and cataracts，respectively. The 100% subjects will not respond or experience adverse reactions to at least one medication. Conclusions The physical examination subjects in this study can benefit to various degrees from WGS. The further promotion of WGS in physical examination population may help with disease prevention and health management throughout their entire life cycle.

Key words: Whole-genome sequencing, Monogenic genetic disease, Physical examination, Health management