Analysis of worldwide carrier frequency and predicted genetic prevalence
of congenital hypothyroidism based on a general population database
Background: 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. Methods: Ten
candidate genes that follow an autosomal recessive inheritance pattern
in congenital hypothyroidism (SLC5A5, TPO, TG, IYD, DUOXA2, DUOX2, TSHR,
TSHB, TRHR, FOXE1) in the gnomAD database (v2.1.1) were analyzed. The
carrier frequency (CF) and predicted genetic prevalence (pGP) were
estimated. Results: The total CF in the overall population was 2.9%.
DUOX2 showed the highest CF (1.46%), followed by TG (0.47%), TPO
(0.42%), TSHR (0.16%), DUOXA2 (0.15%), IYD (0.08%), TRHR (0.07%),
SLC5A5 (0.07%), TSHB (0.04%), and FOXE1 (0%). The pGP in the overall
population was 6.57 individuals per 100.000 births (1:15,216). The
highest pGP was in the East Asian group at 44.65 per 100,000 births
(1:2,240), followed by Finnish (14.21), other (5.99), Non-Finnish
European (5.96), African (3.80), South Asian (3.07), Latino (2.99), and
Ashkenazi Jewish (1.52) groups. Conclusion: The feasibility of genetic
screening for congenital hypothyroidism may be determined by ethnicity.
Comparing the pGP with the real prevalence of congenital hypothyroidism
indicates that genetic screening in East Asian may be feasible.