Two research paths toward identifying schizophrenia risk genes

February 20, 2014, Elsevier

Schizophrenia has long been known to be highly heritable and is present in approximately 1% of the population. Researchers have been following two paths in their pursuit of identifying schizophrenia risk genes.

Initially, they studied common gene variants that, individually, only increase the risk for schizophrenia by a few percent, perhaps increasing the likelihood of developing schizophrenia from a 10 out of a 1000 chance to an 11 or 12 out of a 1000 chance.

More recently, research has identified gene variants that are rare in the population but, when present, more substantially increase the risk for developing schizophrenia. For example, in the current issue of Biological Psychiatry, a large collaborating group of international scientists, led by Dr. Jennifer Mulle, an Assistant Professor at Emory, report a 1.4 megabase duplication on chromosome 7 (7q11.23) that increases the risk for schizophrenia over 10 times, i.e., to 100 out of a 1000 chance (10%).

"We also found it interesting that three different disorders (schizophrenia, autism, and intellectual development) that strike at different times and present in different ways, have genetic links to this same region on chromosome 7," commented Mulle. "Our findings support the notion of a neuro-developmental link between these disorders."

In this same issue, Dr. George Kirov at Cardiff University and colleagues scanned the genome for copy number gene variants, i.e., where abnormal numbers of gene copies exist. They studied 70 of these variants, all previously implicated in schizophrenia and/or early-onset developmental disorders, such as developmental delay, intellectual deficit and autism spectrum disorders (DD/ID/ASD). They then compared the risk for carriers of these variants to develop one or more of these disorders, i.e. their genetic penetrance.

"The result might be unexpected for many: the penetrance for schizophrenia is several times lower than for the group of DD/ID/ASD. The total penetrance for any of these disorders is quite high, ranging from 10% for duplications at 16p13.11 to nearly 100% for the velocardiofacial syndrome region on chromosome 22. These findings will have implications for genetic counselling of carriers," said Kirov.

"It seems that we are at a critical point in the genetics of schizophrenia - the identification of rare gene variants that substantially increase the risk for schizophrenia," said Dr. John Krystal, Editor of Biological Psychiatry. "However, we have a very limited understanding of how these genes alter brain development to produce schizophrenia and other disorders. This knowledge would seem to hold clues about mechanisms of prevention and treatment."

In addition, scientists do not yet understand why the genetics of schizophrenia is not tightly aligned with the symptoms of schizophrenia. In other words, gene variants that increase the risk for increase the risk for other disorders, such as developmental delay, autism, and bipolar disorder.

"The failure of our genome to follow DSM-V is not simply a shortcoming of our diagnostic manual, rather it is yet another reminder that there are fundamental aspects of the biology of psychiatric disorders that we do not understand," added Krystal.

Explore further: New genetic risk factor found for schizophrenia

More information: "Reciprocal Duplication of the Williams-Beuren Syndrome Deletion on Chromosome 7q11.23 Is Associated with Schizophrenia" by Jennifer Gladys Mulle, Ann E. Pulver, John A. McGrath, Paula S. Wolyniec, Anne F. Dodd, David J. Cutler, Jonathan Sebat, Dheeraj Malhotra, Gerald Nestadt, Donald F. Conrad, Matthew Hurles, Chris P. Barnes, Masashi Ikeda, Nakao Iwata, Douglas F. Levinson, Pablo V. Gejman, Alan R. Sanders, Jubao Duan, Adele A. Mitchell, Inga Peter, Pamela Sklar, Colm T. O'Dushlaine, Detelina Grozeva, Michael C. O'Donovan, Michael J. Owen, Christina M. Hultman, Anna K. Kähler, Patrick F. Sullivan, The Molecular Genetics of Schizophrenia Consortium, George Kirov, and Stephen T. Warren. DOI: 10.1016/j.biopsych.2013.05.040

"The Penetrance of Copy Number Variations for Schizophrenia and Developmental Delay" by George Kirov, Elliott Rees, James T.R. Walters, Valentina Escott-Price, Lyudmila Georgieva, Alexander L. Richards, Kimberly D. Chambert, Gerwyn Davies, Sophie E. Legge, Jennifer L. Moran, Steven A. McCarroll, Michael C. O'Donovan, and Michael J. Owen (DOI: 10.1016/j.biopsych.2013.07.022). The articles appear in Biological Psychiatry, Volume 75, Issue 5 (March 1, 2014)

Related Stories

New genetic risk factor found for schizophrenia

August 1, 2013
Researchers at Emory's Rollins School of Public Health have identified a large duplication on chromosome 7q11.23 as a new risk factor for schizophrenia.  (7q11.23 refers to the specific location of the duplicated region ...

New risk factor found for schizophrenia

February 6, 2014
(Medical Xpress)—Scientists have discovered a link between a largely unstudied gene and schizophrenia.

Genetic risk for schizophrenia is connected to reduced IQ

May 16, 2013
The relationship between the heritable risk for schizophrenia and low intelligence (IQ) has not been clear. Schizophrenia is commonly associated with cognitive impairments that may cause functional disability. There are clues ...

Jumping DNA in the brain may be a cause of schizophrenia

January 2, 2014
Stretches of DNA called retrotransposons, often dubbed "junk DNA", might play an important role in schizophrenia. In a study published today in the journal Neuron, a Japanese team revealed that LINE-1 retrotransposons are ...

Researchers uncover impact of mutations in the human genome on cognitive ability

December 19, 2013
deCODE genetics reported today in the journal Nature that mutations associated with an increased risk of schizophrenia and autism also affect cognition in individuals without the disease or intellectual disability. The research ...

Does immune dysfunction contribute to schizophrenia?

October 10, 2012
A new study reinforces the finding that a region of the genome involved in immune system function, called the major histocompatibility complex (MHC), is involved in the genetic susceptibility to schizophrenia.

Recommended for you

Researchers identify gene responsible for mesenchymal stem cells' stem-ness'

January 22, 2018
Many doctors, researchers and patients are eager to take advantage of the promise of stem cell therapies to heal damaged tissues and replace dysfunctional cells. Hundreds of ongoing clinical trials are currently delivering ...

Genes contribute to biological motion perception and its covariation with autistic traits

January 22, 2018
Humans can readily perceive and recognize the movements of a living creature, based solely on a few point-lights tracking the motion of the major joints. Such exquisite sensitivity to biological motion (BM) signals is essential ...

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.