Women Have More Gene Copy Number Variations Than Men, But This Doesn’t Increase Schizophrenia Risk as Expected

Women Have More Gene Copy Number Variations Than Men, But This Doesn’t Increase Schizophrenia Risk as Expected

Posted: July 27, 2016
Women Have More Gene Copy Number Variations Than Men

Although women show more of a certain type of genetic mutation linked to schizophrenia than do men, that pattern does not influence their risk of developing the illness, researchers have found.

A team of researchers at Cardiff University looked at people with and without schizophrenia to compare cases of a genetic phenomenon called copy number variations, or CNVs. These variations are sections of the human genome that either get deleted or duplicated in different numbers across individuals. The consequence of having a CNV is that one is either missing a protein or proteins encoded by genes in the deleted region, or one can have “extra” amounts of certain proteins, due to duplication of genes in a given CNV. Everyone has CNVs, but an unlucky few have them in parts of the genome where they adversely affect genes linked to illness.

Both deletions and duplicates were examined by the team, which was led by Dr. Elliott Rees of Cardiff University, Wales, and included 2012 NARSAD Sidney R. Baer Prizewinner and 2009 Young Investigator grantee James T.R. Walters, M.D., Ph.D; 2012 Lieber Prizewinner Michael O’Donovan, M.D., Ph.D.; and 2012 Lieber Prizewinner Michael Owen, M.D., Ph.D.

Reporting their findings online May 17 in Scientific Reports, the team confirmed findings from past studies that women without diagnosed psychiatric disorders have more CNVs than men—specifically, more deletions than duplicates. They also report for the first time that women with schizophrenia have more of these variants across the genome, and also at 11 locations in the genome where variants have previously been linked to risk for schizophrenia. Yet this higher incidence of CNVs, the researchers concluded, did not make the women more or less likely to have a schizophrenia diagnosis. This finding suggests that gender does not impact the relationship between CNVs and schizophrenia.

However, the researchers suggested that higher numbers of CNVs among women may reflect the fact that they are in some way protected against some illnesses, such as schizophrenia. Women without schizophrenia showed significantly higher numbers of rare, large CNVs, or variants that occupy bigger chunks of the genome. This is precisely the type of CNV that previously has been linked to other neurodevelopmental disorders that are diagnosed less frequently in women than men, such as autism spectrum disorder and intellectual disability. But more research is needed to investigate these possible protective effects, the team says.

Women Have More Gene Copy Number Variations Than Men Wednesday, July 27, 2016

Although women show more of a certain type of genetic mutation linked to schizophrenia than do men, that pattern does not influence their risk of developing the illness, researchers have found.

A team of researchers at Cardiff University looked at people with and without schizophrenia to compare cases of a genetic phenomenon called copy number variations, or CNVs. These variations are sections of the human genome that either get deleted or duplicated in different numbers across individuals. The consequence of having a CNV is that one is either missing a protein or proteins encoded by genes in the deleted region, or one can have “extra” amounts of certain proteins, due to duplication of genes in a given CNV. Everyone has CNVs, but an unlucky few have them in parts of the genome where they adversely affect genes linked to illness.

Both deletions and duplicates were examined by the team, which was led by Dr. Elliott Rees of Cardiff University, Wales, and included 2012 NARSAD Sidney R. Baer Prizewinner and 2009 Young Investigator grantee James T.R. Walters, M.D., Ph.D; 2012 Lieber Prizewinner Michael O’Donovan, M.D., Ph.D.; and 2012 Lieber Prizewinner Michael Owen, M.D., Ph.D.

Reporting their findings online May 17 in Scientific Reports, the team confirmed findings from past studies that women without diagnosed psychiatric disorders have more CNVs than men—specifically, more deletions than duplicates. They also report for the first time that women with schizophrenia have more of these variants across the genome, and also at 11 locations in the genome where variants have previously been linked to risk for schizophrenia. Yet this higher incidence of CNVs, the researchers concluded, did not make the women more or less likely to have a schizophrenia diagnosis. This finding suggests that gender does not impact the relationship between CNVs and schizophrenia.

However, the researchers suggested that higher numbers of CNVs among women may reflect the fact that they are in some way protected against some illnesses, such as schizophrenia. Women without schizophrenia showed significantly higher numbers of rare, large CNVs, or variants that occupy bigger chunks of the genome. This is precisely the type of CNV that previously has been linked to other neurodevelopmental disorders that are diagnosed less frequently in women than men, such as autism spectrum disorder and intellectual disability. But more research is needed to investigate these possible protective effects, the team says.