Is Schizophrenia Genetic?

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Schizophrenia is a severe mental health condition that is characterized by hallucinations, delusions, and disorganized speech. This condition can lead to significant disability for some people if left untreated. The causes of schizophrenia are multifactorial and actively researched, but existing research indicates that there are genetic risk factors for schizophrenia.

The heritability of schizophrenia has been found to range between 60-80%. However, just because a relative has schizophrenia does not mean you will develop it. Many factors outside genetics cause schizophrenia, include gene-gene, gene-environment, and environment-environment interactions.

Schizophrenia affects approximately 1% of people worldwide. There is ongoing research into its causes.

Genetic Causes

The genetics behind schizophrenia is complex. Schizophrenia is considered to be polygenic, meaning that there is no one single gene that causes this condition.

Instead, researchers have found many different genes and loci that can increase the chance of developing schizophrenia. Each of these gene variants increases schizophrenia predisposition a small amount, and many gene variants in combination increase risk further.

Genome-wide association studies have helped connect specific genetic variants with schizophrenia. Of these, a 2014 meta-analysis by the Schizophrenia Working Group is the most extensive genetic study. This study found 108 genetic loci that are associated with schizophrenia.

Of these 108 loci, the genes have implications for calcium channel regulation, immunity, dopamine synthesis, and glutamate neuroreceptors.

It's important to note that a locus is a genomic region or location on a chromosome where a gene is. Of the 108 loci associated with schizophrenia, over 600 genes are implicated. Researchers encourage caution when making conclusions on these 600 genes.

22q11.2 deletion

The genetic variations associated with schizophrenia include duplications, deletions, and microdeletions. One of the most-studied deletions with a high rate of schizophrenia is the 22q11.2 deletion syndrome. It's estimated that about 22% of people with this deletion have schizophrenia.

DRD2 variant

Research indicates that the His313 polymorphism in the DRD2 gene is linked to schizophrenia. This gene is involved in dopamine receptor signaling.

ZNF804A variant

ZNF804A, a zinc finger protein gene that is most active prenatally, has been described as a schizophrenia risk gene. The rs1344706 polymorphism of this gene is associated with schizophrenia susceptibility.

There is much research that still needs to be done regarding the genetics of schizophrenia. Currently, we don't know if certain genetic variants relate to certain clinical features of schizophrenia. We also can only make conclusions on genes increasing schizophrenia risk; no Mendelian inheritance or single-gene cause has been identified.

Chance of Developing Schizophrenia

Schizophrenia is highly heritable. There are estimates that the condition is 60-80% heritable.

A person's chance of developing schizophrenia increases with the nearness of relation that has schizophrenia. For example, having a parent with schizophrenia increases a person's risk 10 times the population risk of 1%. Those with both parents having schizophrenia are at 40 times the risk of developing it than the general population.

Twin studies are an important tool in how scientists research and make conclusions on the impact of genes and heredity because they can examine identical twins (who share 100% of DNA) and fraternal twins (who share 50% of DNA).

A 2018 nationwide twin study in Denmark found that the concordance rate or percentage who both had schizophrenia in identical twins was 33%. It was 7% in fraternal twins. The heritability of schizophrenia in this study was estimated to be 79%.

However, the relatively low rate (33%) of concordance in identical twins indicates that other factors besides genetics are at play in schizophrenia development.

Most of the research on the genetics of schizophrenia has been performed on European-ancestry participants. This means the generalizability of these findings across global populations is questionable.

One recent 2019 study on over 57,000 East Asian ancestry participants concluded that genetic risk factors are consistent across populations, but more research on varying populations is needed.

Genetic vs. Environmental Factors

Although research has found a significant genetic risk factor to schizophrenia, it is not currently possible to make predictions based on genetics as to who will ultimately develop schizophrenia.

Genome-wide association studies explain a minority of schizophrenia occurrences. Many researchers believe that gene-environment interaction has a significant role in schizophrenia development.

In other words, a person may be predisposed to develop schizophrenia due to their genes, but wouldn't necessarily develop the condition without the additional input from environmental risk factors.

Environmental factors that have been shown to increase schizophrenia risk include:

  • Pregnancy and birth complications
  • Viral infections
  • Advanced parental age
  • Trauma
  • Social adversities or disadvantages
  • Isolation
  • Migration
  • Urbanicity
  • Cannabis or other substance use

Ultimately, there is still much research to be done on the causes of schizophrenia, including both environmental and genetic factors. The genetics of schizophrenia is an active and ongoing area of research, including investigation of genetic therapeutics to help treat this severe mental health condition.

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