Lack of association of TP73 rare variants with amyotrophic lateral sclerosis in a Chinese cohort

Background Recently, several rare variants of TP73 were identified as potential disease cause for amyotrophic lateral sclerosis (ALS) in the European population. However, further replication was still necessary, especially in cohorts with different ethnic backgrounds. Methods To explore the genetic role of TP73 in ALS in the Asian population, we analyzed the rare protein-coding variants in 2011 patients with ALS and 3298 controls with whole-exome sequencing. Fisher's exact test was performed between each variant and disease risk, while at gene level over-representation of rare variants in patients was examined with optimized sequence kernel association test. Results Totally 24 rare variants with minor allele frequency < 0.01 were identified, among which nine were absent in controls. One variant p.P335T was previously reported, and another three variants were in the same amino acids as the variants reported in previous studies (p.R36Q, p.R414Q, p.R78C). At gene level, rare variants of TP73 were not enriched in patients. Conclusions Our findings did not support the genetic role of TP73 in ALS in the Chinese population. Replication of specific variants identified in patients from different cohorts might provide additional insight. The current results also broadened the mutation spectrum of TP73 and paved the way for further research.

Automated summary

This study aimed to explore the genetic role of TP73 in amyotrophic lateral sclerosis (ALS) in the Asian population. Through the analysis of rare protein-coding variants, it was found that TP73 did not play a genetic role in ALS in the Chinese population. Replication studies of specific variants identified in patients from different populations may provide additional insights. Additionally, this study broadened the mutation spectrum of TP73 and paved the way for further research.