Higher Genetic Risk for ALS Linked to Poorer Verbal, Numerical Skills in Adults in UK Study

A high genetic risk for amyotrophic lateral sclerosis (ALS), assessed using so-called polygenic risk scores,  was linked in a study to poorer performances on verbal and numerical tests in otherwise healthy adults, but not to physical disabilities.

The study, “Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function,” was published in the journal PLOS One.

Researchers are increasingly using these risk scores to better understand complex genetic diseases like ALS.

Polygenic risk scores summarize data from large genome-wide (complete set of DNA) screen studies that identify genetic risk factors linked to a certain disease. While genetic risk may not signify much on its own, the polygenic risk score is able to combine thousands of genetic variants and be used to predict the risk for a range of complex traits and diseases.

Researchers at the University of Edinburgh evaluated whether the polygenic risk for ALS, as well as Alzheimer’s disease and frontotemporal dementia (FTD), associates with cognitive performance or physical abilities known to be affected by the loss of nerve cells.

They analyzed data from the UK Biobank study, used to identify factors underlying human diseases in healthy adults.

“A total 502,655 community-dwelling participants aged between 37 and 73 years were recruited between 2006 and 2010 in the United Kingdom, and underwent extensive baseline testing including cognitive and physical assessments,” the researchers wrote.

Participants were tested for their cognitive skills using five different tests — verbal-numerical reasoning, reaction time, memory, trail making, and symbol digit substitution.

The verbal-numerical reasoning test consisted of a 13-item questionnaire assessing verbal and numerical thinking.

Participants also underwent a series of tests for signs of muscle weakness and respiratory problems, two symptoms characteristic of ALS and some FTD patients.

Results showed that adults with a higher polygenic risk for ALS had only one significant link to poorer cognitive skills, that of verbal-numerical reasoning.

FTD patients with higher polygenic risk scores, in contrast, took longer to complete the trail making test, which evaluates visual attention and task switching capacities. But they had better lung function, as shown by higher scores in forced expiratory volume in 1s (FEV1) and peak expiratory flow (PEF).

High polygenic risk for Alzheimer’s disease was associated with impairments in several tests of cognitive functions — verbal-numerical reasoning, memory, symbol digit substitution and the trail making test. These adult, overall, had the worse results.

“Our results showed a novel relationship between cognitive and physical function variables and polygenic risk for neurodegenerative conditions in a healthy population, particularly in the case of AD [Alzheimer’s’ disease],” the researchers wrote.

They concluded: “[T]he findings of this study demonstrate that polygenic risk for ALS is associated with verbal-numeric reasoning, while polygenic risk for FTD was associated with executive functioning. Physical function measures commonly affected in patients with ALS, were not associated with polygenic risk of ALS in healthy adults.”