ALS and schizophrenia appear to be very different diseases. However, McLaughlin and colleagues have recently found a 14.3% overlap in the genetics of ALS and schizophrenia.
On the surface, amyotrophic lateral sclerosis (ALS) and schizophrenia appear to be very different. In ALS, the neurons that help us move our muscles gradually die. Neuron death results in weakness, difficulty breathing and swallowing, and eventually, death. In schizophrenia, individuals experience many symptoms involving their thoughts and behavior. These include false beliefs, hallucinations, poor function in social contexts, and depression. However, people whose relatives have ALS are at higher risk of schizophrenia, and ALS often involves symptoms similar to those of schizophrenia. Genes play a large role in both diseases, leading researchers to investigate whether there are genetic links between the two.
In a recently published paper in Nature Communications, McLaughlin and colleagues investigated the genetics of ALS and schizophrenia using a genome-wide association study (GWAS). In GWAS, researchers look at the genetic code of thousands of people, looking for links between diseases and particular gene variants. In this particular study, researchers are looking for pleiotropy, a state in which single genes can affect many traits. This happens when a single gene encodes a protein or other molecular structure that acts in many tissues or that interacts with other proteins.
McLaughlin and colleagues included genomic data from over 100,000 European and Asian individuals in their study. Over 36,052 had ALS and 79,845 had schizophrenia, and the control group totaled at least 5,582 individuals. Diagnoses were performed using strict protocols, so it is unlikely that this sample includes misdiagnoses. The researchers estimated the correlation of shared genetic variants to disease traits between the groups.
Based on their study, McLaughlin and colleagues concluded that ALS and schizophrenia share a 14.3% genetic correlation. This means that there is about 14.3% overlap in the genes influencing both diseases. This confirms results from another smaller study focusing on European individuals. One of the genes, linked to both ALS and schizophrenia, helps regulate development of neurons. The researchers found no genetic correlation between ALS and other mental illnesses, supporting a unique relationship between ALS and schizophrenia. In addition, the researchers identified five new genes that are linked to ALS.
Future work will aim to identify rare genetic variants that are involved in ALS and schizophrenia. Ideally, researchers would find a large sample of individuals with both diseases. Further research to clarify the biological processes that these genes regulate is also needed so that these findings can be translated into treatment.
Written By: C.I. Villamil