Analysis of Worldwide Carrier Frequency and Predicted Genetic Prevalence of Autosomal Recessive Congenital Hypothyroidism Based on a General Population Database.

Kyung-Sun Park

doi:10.3390/genes12060863

Abstract

To assess how genomic information of the general population reflects probabilities of developing diseases and the differences in those probabilities among ethnic groups, a general population database was analyzed with an example of congenital hypothyroidism. Twelve candidate genes that follow an autosomal recessive inheritance pattern in congenital hypothyroidism (SLC5A5, TPO, TG, IYD, DUOXA2, DUOX2, TSHR, SLC26A7, GLIS3, FOXE1, TSHB, TRHR) in the gnomAD database (v2.1.1) were analyzed. The carrier frequency (CF) and predicted genetic prevalence (pGP) were estimated. The total CF in the overall population was 3.6%. DUOX2 showed the highest CF (1.8%), followed by TG (0.46%), TPO (0.44%), TSHR (0.31%), SLC26A7 (0.144%), DUOXA2 (0.141%), IYD (0.08%), SLC5A5 (0.06%), TRHR (0.059%), GLIS3 (0.059%), TSHB (0.04%), and FOXE1 (0%). The pGP in the overall population was 10.01 individuals per 100,000 births (1:9992). The highest pGP was in the East Asian population at 52.48 per 100,000 births (1:1905), followed by Finnish (35.96), Non-Finnish European (9.56), African/African American (4.0), Latino/Admixed American (3.89), South Asian (3.56), and Ashkenazi Jewish (1.81) groups. Comparing the pGP with the real incidence of congenital hypothyroidism, the pGP in East Asian populations was highly consistent with the real incidence.

Highlights

Genetic screening is a type of genetic testing that is designed to identify a specified population at a higher risk of having or developing a disease with the aim of prevention or early treatment [1]
Comparing the predicted genetic prevalence (pGP) with the real incidence of congenital hypothyroidism, the pGP in East Asian populations was highly consistent with the real incidence
Genomic data associated with congenital hypothyroidism, which is one of the major achievements of preventive medicine [4], were analyzed based on the general population database, and their carrier frequency and genetic prevalence were estimated by population

Summary

Introduction

Genetic screening is a type of genetic testing that is designed to identify a specified population at a higher risk of having or developing a disease with the aim of prevention or early treatment [1]. Genetic screening is performed as targeted testing for known hotspot variations. Several companies have launched proactive genetic testing for generally healthy individuals without a personal or family history using NGS techniques for identifying particular genes or performing whole exome/genome sequencing that is not confined to hotspot variations. Additional questions are the use of genetic testing to provide useful and crucial information and eventually prevent diseases in healthy individuals. To answer these questions, genomic data associated with congenital hypothyroidism, which is one of the major achievements of preventive medicine [4], were analyzed based on the general population database, and their carrier frequency and genetic prevalence were estimated by population

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Discussion

Conclusion