Sex-specific risk loci and modified MEF2C expression in ALS

Ross Patrick Byrne; Wouter van Rheenen; Tomás DS Gomes; Ciaran Michael Kelly; Emrah Kacar; Ahmad Al Khleifat; Alfredo Iacoangeli; Ammar Al‐Chalabi; Jan Herman Veldink; Russell Lewis McLaughlin

doi:10.1101/2024.05.25.24307829

Genetic & Genomic MedicinemedRxivMay 25, 2024

Preprint

Sex-specific risk loci and modified MEF2C expression in ALS

Ross Patrick Byrne iD, Wouter van Rheenen iD, Tomás DS Gomes iD, Ciaran Michael Kelly iD, Emrah Kacar iD, Ahmad Al Khleifat iD, Alfredo Iacoangeli iD, Ammar Al‐Chalabi iD, Jan Herman Veldink iD, Russell Lewis McLaughlin iD

Abstract

Significantly more men develop amyotrophic lateral sclerosis (ALS) than women, and heritability is not uniform between male and female transmissions, together suggesting a role for sex in the genetic aetiology of the disease. We therefore performed sex-stratified genome-wide and transcriptome-wide analyses of ALS risk, identifying six novel sex-specific risk loci including MEF2C, which shows increased expression in female ALS motor neurones. X-chromosome analysis revealed an additional risk locus at IL1RAPL2.

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