Common Gene Mutations May Link ALS and Schizophrenia, Study Reports

Common Gene Mutations May Link ALS and Schizophrenia, Study Reports

Amyotrophic lateral sclerosis (ALS) and schizophrenia may be caused by similar gene mutations that affect the way neurons work, according to new research.

Researchers found that 14.3 percent of the genetic variations linked to ALS were also present in people with schizophrenia, suggesting the diseases may be related.

The study, “Genetic Correlation Between Amyotrophic Lateral Sclerosis And Schizophrenia,” was published in the journal Nature Communications.

Schizophrenia, a psychiatric disorder, is characterized by persistent mental illness that affects a person’s behavior, thinking, and emotions. Symptoms can include hallucinations and delusions, reduced motivation, poor cognitive abilities and social interaction difficulties.

Both ALS and schizophrenia are caused by genetic mutations, meaning they can strike people in different generations of the same family. Previous research has shown that the incidence of schizophrenia can be high in relatives of ALS patients, again suggesting a relationship between the two.

“There is evolving clinical, epidemiological and biological evidence for an association between ALS and psychotic illness, particularly schizophrenia,” the researchers wrote.

The team investigated the possibility of a genetic connection by analyzing the genes of more than 100,000 individuals, and relating the findings with the presence or absence of each disease in these people.

A significant overlap was seen, with researchers estimating the genetic correlation to be 14.3 percent. This indicates that certain genes associated with increased risk are common between ALS and schizophrenia, and that the diseases share common biological mechanisms.

Indeed, although both diseases are clinically different — one is a mental illness and the other mainly a motor disease — both may be triggered by mutations in genes that affect the functioning of neurons. These genes include known ALS genes, such as C9orf72, but also five newly associated genes: CNTN6, TNIP1, PPP2R2D, NCKAP5L and ZNF295-AS1. All of these genes — along with others either known or yet to be identified — may underlie a  shared mechanism between ALS and schizophrenia.

Researchers found no association between ALS and other neuropsychiatric conditions, such as bipolar disorder, autism and major depression, but recommended studies with larger populations to confirm their finding.

“As both ALS and schizophrenia are [different] conditions, further [genetic], biological and clinical studies are likely to yield novel insights into the pathological processes for both diseases and will provide clinical [distinction] parameters that could drive novel drug development for both neurodegenerative and psychiatric conditions,” the researchers concluded.


  1. This was a great article. I so would have enjoyed seeing it published 10 years ago.
    It’s interesting that only a handful of related genes are listed above. But research that’s been around for quite some time supports this notion and other genes. It’s always a race to find a new gene around here…if only we helped people today with the ones we already know they have!
    For example, the MTHFR A1298C variation is shown to be a gender-associated risk factor (in women) for ALS where the very same gene in men is shown to be a gender risk-factor for schizophrenia…low MTHFR is a cycling disease-state, with enzyme activity that fluctuates based upon stressors like nutrition, infection, toxic exposures, seasons, etc. and is intimately linked to BH4 recycling.
    I am confident that there are countless more genes that simultaneously work together to create the neurotoxic continuum (particularly the link between ALS and schizophrenia). Of these known gene mutations, gene deletions, variations, and related conditions, they are largely referred to as toxic schizophrenias (that overlap with neurodegenerative disease like ALS). Genes for impaired detox are rather common and very ill people often cary many such SNPs or mutations. However, the spectrum of presentation (schizophrenia versus ALS) can be attributed partially to both environmental exposures and other gene variations carried by individuals (protective and detrimental genetic variations). It is of note that where one gene that promotes central nervous system detox is missing (a gene deletion) or when a detox enzyme is reduced, another gene is able to pick up the slack. But, some people won’t have the second gene that the body has already in place to compensate. This is also just one scenario that explains that varying neurotoxic presentations (from ALS to schizophrenia)…and lets call a spade a spade…Parkinson’s and Dementia fit along this spectrum too (though perhaps larger population studies are needed).
    The “detoxigenomic” gene text kit is a wonderful place to become an active participant in one’s self-care (enlightening information that can be used to empower one another, not throw in the towel and spend that savings on ethically questionable research programs). I personally use copious amounts of the world’s best Phase II detoxifiers (Liquid, stabilized, enhanced, purified, bioavailable R-lipoic Acid and stabilized, enhance BioCurcumin) to support metabolism and detox (and related cascade of damages) with my products from GeroNova Research. This has been instrumental in my formerly neurotoxic life…
    Really, the whole one-gene equals one-disease is absurd. That kind of reductionism is reserved for gene modeling in animals. It does not reflect what is seen in complex humans.
    Good article…better done 10+ years ago…It’s something…but is it empowering? Does this article make me want to run out and do everything to save my life? What does it do to your sense of empowerment? I want to be empowered.

    • Ally says:

      Hi, Angeline – You seem to know a lot about this, so I was wondering if you could help me understand – I read the same study you are referring to, and am homozygous for the C677t gene. I am really scared – does this mean I am destined to get ALS? Or, is it the homocysteine levels that is the problem? Appreciate any insight…

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