Indian origin scientist identifies nine markers that increase schizophrenia risk

December 4th, 2007 - 2:37 pm ICT by admin  

Washington , Dec 4 (ANI): A study led by an Indian-origin researcher has identified nine genetic markers that augment a persons risk for schizophrenia, thereby unearthing original evidence that this disabling brain disease can be inherited in a recessive manner.

A recessive trait is one that is inherited from both parents.

The study was led by Anil Malhotra, MD, director of psychiatric research at Zucker Hillside and senior investigator of the study. The lead author of the study was Todd Lencz, PhD, associate director of research at Zucker Hillside Hospital campus of the Feinstein Institute for Medical Research.

If a person inherits identical copies of these markers from each parent, his or her risk for schizophrenia increases substantially, said Dr. Lencz.

If these results are confirmed, they could open up new avenues for research in schizophrenia and severe mental illness, said Anil Malhotra.

The scientists developed a complex mathematical approach called whole genome homozygosity association (WGHA) that offered a novel way of examining genetic information.

It makes it possible for the scientists to simultaneously look at genetic information derived from the patients mother and father, and identify identical pieces of chromosomes. They tested genetic material from 178 patients and 144 controls.

The prevailing view in psychiatric genetics has been that there are probably dozens, if not hundreds, of genetic variations that could lead to schizophrenia, but each gene has a small effect.

It is the wrong mix of many genes, plus unknown environmental stressors, that activate the onset of symptoms.

Almost, one in every 100 people suffer from schizophrenia, a condition marked by episodes of hallucinations, delusions and disordered thinking.

However, at least for a subset of patients, the new findings suggest another scenario.

The researchers identified nine regions along the chromosomes that might have a larger role to play in triggering the disease when two identical variants are inherited.

Four of these regions contain genes that have been associated with schizophrenia in the past, giving validation for the technique. The remaining five regions provide a supplementary set of newly discovered genetic risk factors.

Many genes found in these regions are associated with the structure and survival of neurons.

In genetic parlance, several of these markers demonstrated high penetrance, meaning that their effect on disease risk was large.

In the study, 81 percent of the schizophrenia patients had at least one of these recessive markers, compared to only 45 percent of the normal control group. Nearly half of the patients had two or more compared to 11 percent of the controls. And while no one in the healthy group had identical chunks of chromosomes in four or more of these risk regions, subjects with more than three demonstrated a 24-fold increased risk of developing schizophrenia.

This type of analysis could greatly improve our ability to diagnose schizophrenia and clarify specific subtypes of patients. The critical next step is confirming these results in independent datasets, said, Dr. Lencz.

What is most exciting is that the study implicates new genes in schizophrenia, said David Goldman, MD, chief of laboratory of neurogenetics at the National Institute on Alcohol Abuse and Alcoholism.

He added: Now, they have to trace down the genes that mediate this vulnerability.

The scientists said that identifying these novel genes will help improve understanding of the disease in the long run and lead to the development of more effective treatments.

The study was published in the Proceedings of the National Academy of Sciences. (ANI)

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