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Clinical and Research News
Schizophrenia Risk Found in Mother-Daughter Gene Pair
Psychiatric News
Volume 41 Number 21 page 30-30

A genetic match between a mother and fetus may actually increase risk of schizophrenia.

UCLA scientists have discovered that daughters who have a specific immune-system gene that too closely matches their mothers' are more likely to develop schizophrenia later in life.

Normally, it's a good thing when the genes in question match: after all, they are responsible for the body's ability to “identify self.”

The team of researchers, led by Christina Palmer, Ph.D., an associate professor of psychiatry and human genetics at UCLA, focused on HLA-B, one of a family of genes called the human leukocyte antigen (HLA) complex. HLA helps the immune system distinguish the body's own proteins from those made by foreign invaders, such as viruses and bacteria.

The report appeared in the October American Journal of Human Genetics. The study was funded by the National Institute of Mental Health, the Center of Excellence in Disease Genetics of the Academy of Finland, and the University of Helsinki's Biocentrum-Helsinki research consortium.

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The researchers studied a group of 274 Finnish families in which at least one child had been diagnosed with schizophrenia or a related psychosis. Within this group, 484 offspring had been diagnosed with schizophrenia, schizoaffective disorder, or schizophrenia spectrum disorders. Subjects were born between 1940 and 1976.

The scientists drew blood samples from those with schizophrenia and all available family members, including siblings and parents. DNA analysis was then used to identify families in which the children's HLA-B gene closely matched their mothers' and those in which the HLA-B genes were mismatched.

Analysis of the entire sample revealed that daughters whose HLA-B gene matched their mothers' were 1.7 times more likely to develop schizophrenia than children whose gene didn't match their mothers'. The researchers then calculated that if this genetic risk due to matching could have been avoided (for example, through genetic counseling), up to 12 percent of the cases of schizophrenia in daughters could have been prevented.

In fact, determining a patient's HLA gene makeup is routinely used to assess clinical risks, and that process is commonly known as “tissue typing.” Because the HLA complex controls the immune system's“ recognition of self,” HLA typing of a transplant recipient must closely match the HLA gene typing of donated organ tissue. If a donated organ's HLA complex contains a high number of individual genes not found in the recipient, the risk of rejection increases dramatically.

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“Normally, the body would reject a [transplanted] organ that isn't the same HLA typing as self, but for reasons that are not well understood, a mother's body does not reject a fetus when that fetus is of a different HLA typing,” explained Palmer, who is also a staff researcher at the Semel Institute for Neuroscience and Human Behavior.

“It seems pretty clear that it's a good thing for the HLA genes of a mother and her fetus to not match,” she added. “We suspect that HLA matching increases a woman's susceptibility to pregnancy complications, which in turn predisposes her child to schizophrenia. This is one more piece in the puzzle of identifying genetic markers for the disease.”

“Our current findings clearly suggest that schizophrenia risk rises, especially in daughters, when the child's HLA-B gene too closely matches its mother's,” Palmer told Psychiatric News. “We don't know whether sons who match are not affected, or maybe sons are affected and are so compromised that they are less likely to come to term.”

“In the future, we also may be able to produce tailored risk assessments for individuals with personal or family histories of schizophrenia,” said Palmer.

An abstract of “HLA-B Maternal-Fetal Genotype Matching Increases Risk of Schizophrenia” is posted at<www.journals.uchicago.edu/AJHG/journal/issues/v79n4/43692/brief/43692.abstract.html>.

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