# Genetic Modifiers of ALS: The Impact of Chromogranin B P413L in a Bulgarian ALS Cohort

## TL;DR

This study found that a genetic variant in the CHGB gene is more common in Bulgarian patients with a type of motor neuron disease called ALS, suggesting it may increase disease risk.

## Contribution

The study identifies a novel association between the CHGB P413L variant and sporadic ALS in a Bulgarian cohort.

## Key findings

- The minor T allele of CHGB P413L was more frequent in sALS patients than in control groups.
- Carriers of the T allele showed a statistically significant increase in sALS susceptibility compared to non-Finnish Europeans.
- The effect of the variant on age of onset remains uncertain due to a small sample size of carriers.

## Abstract

This study investigated the role of the CHGB P413L variant (rs742710) in sporadic amyotrophic lateral sclerosis (sALS) within the Bulgarian population. We analyzed 150 patients with sALS (85 male and 65 female) for the presence of this variant, its potential impact on disease susceptibility, and age of onset. Genotyping was performed using PCR amplification and direct Sanger sequencing. Statistical analyses included comparisons with control data from GnomAD v2.1.1, one-way ANOVA, and Kaplan–Meier survival analysis. Results revealed a higher frequency of the minor T allele in patients with sALS compared to all control groups and a statistically significant increase in carrier genotypes compared to non-Finnish Europeans (χ2 = 15.4572, p = 0.000440). However, the impact on age of onset was less clear, with no statistically significant differences observed across genotypes or between carriers and non-carriers of the T allele. Kaplan–Meier analysis suggested a potential 2.5-year-earlier onset in T allele carriers, but the small sample size of carriers limits the reliability of this finding. Our study provides evidence for an association between the CHGB P413L variant and sALS susceptibility in the Bulgarian population, while its effect on age of onset remains uncertain, highlighting the need for further research in larger, diverse cohorts.