Genetic identification of familial hypercholesterolemia within whole genome sequences in 6820 newborns

Abstract Familial hypercholesterolemia (FH) is defined as a monogenic disease, characterized by elevated low‐density lipoprotein cholesterol (LDL‐C) levels. FH remains underdiagnosed and undertreated in Chinese. We whole‐genome sequenced 6820 newborns from Qingdao of China to investigate the FH‐related gene ( LDLR , APOB , PCSK9 ) mutation types, carrier ratio and genotype–phenotype correlation. In this study, the prevalence of FH in Qingdao of China was 0.47% (95% CI: 0.32%–0.66%). The plasma lipid levels of FH‐related gene mutation carriers begin to increase as early as infant. T‐CHO and LDL‐C of FH infants was higher by 48.1% ( p < 0.001) and 42.9% ( p < 0.001) relative to non‐FH infants. A total of 22 FH infants and their parent participate in further studies. The results indicated that FH infant parent noncarriers have the normal plasma lipid level, while T‐CHO and LDL‐C increased in FH infants and FH infant parent carriers, but no difference between the groups. This highlights the importance of genetic factors. In conclusion, the spectrum of FH‐causing mutations in the newborns of Qingdao, China was described for the first time. These data can serve as a considerable dataset for next‐generation sequencing analysis of the Chinese population with FH and potentially helping reform regional policies for early detection and prevention of FH.