Allan F McRae

Abstract Pleiotropic conflict, where a genetic locus has antagonistic effects on different traits, is a common phenomenon observed in animals and plants. While pleiotropy has been widely reported in humans, there is no systematic study of pleiotropic conflict in humans. Here, we leverage summary statistics from genome-wide association studies of complex diseases and traits derived from large-scale population cohorts to identify pleiotropic regions with conflicting effects.

Abstract While the p-value threshold of 5.0 x 10-8 remains the standard for genome-wide association studies (GWAS) in humans and other species, it still needs to be updated to reflect the current era of large-scale GWAS, where tens of thousands of sample sizes are used to discover genetic associations at loci with smaller minor allele frequencies.

INTRODUCTION The pathophysiological mechanisms underlying the development of amyotrophic lateral sclerosis (ALS) appear to be complex, mediated by a complex interaction between genetic, epigenetic and environmental (exposome) factors, resulting in dysfunction of critical molecular pathways and neurodegeneration [1-5].