Autism risk is 'mostly genetic,' according to statistical analysis

Researchers claim that nearly 60% of autism risk is genetic, with the implicated variant genes being common among the general population. They publish the results of their research in the journal Nature Genetics.

Autism is widely believed to be caused by an interplay of genetics and other factors. However, scientists have not reached a consensus on how much of an influence genes have on autism risk.

"We show very clearly that inherited common variants comprise the bulk of the risk that sets up susceptibility to autism," say the researchers.

Recent evidence has suggested that the genomes of people who have autism are more likely to include de novo mutations - rare and spontaneous mutations with significant effects that are thought to account for particular cases of autism.

"Many people have been focusing on de novo mutations, such as the ones that can occur in the sperm of an older father," explains Joseph D. Buxbaum, PhD, the study's lead investigator and director of the Seaver Autism Center for Research and Treatment and professor of psychiatry,neuroscience and genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai.

"While we find these mutations are also key contributors, it is important to know that there is underlying risk in the family genetic architecture itself."

By conducting a "rigorous analysis" of DNA sequence variations as part of the Population-Based Autism Genetics and Environment Study (PAGES) Consortium, Dr. Buxbaum's team found that about 52.4% of autism cases can be traced back to both common and rare inherited variations. By contrast, spontaneous mutations were found to account for just 2.6% of total autism risk.

"We show very clearly that inherited common variants comprise the bulk of the risk that sets up susceptibility to autism," Dr. Buxbaum says. "But while families can be genetically loaded for autism risk, it may take additional rare genetic factors to actually produce the disorder in a particular family member."

The study used data from Sweden's universal health registry to compare about 3,000 participants, including autistic subjects and a control group. The researchers say that PAGES is the largest study of its kind to date.

New statistical methods promise 'more reliable results'

Limitations in sample size have previously made it difficult to ascertain the relative influence of common, rare inherited and rare spontaneous variations. Differences in the statistical models and methods used across studies have also presented challenges in obtaining a consensus view, with estimates of autism heritability varying from 17-50%.

In PAGES, new statistical methods - such as "machine learning techniques and dimension reduction tools" - were deployed, which the researchers claim allowed a more reliable method for assessing heritability.

The researchers were also able to access data from a parallel study of Swedish families that looked at twins, cousins, age of the father at birth and the psychiatric history of the parents.

Thomas Lehner, chief of the National Institute of Mental Health's Genomics Research Branch, says:

"This is a different kind of analysis than employed in previous studies. Data from genome-wide association studies was used to identify a genetic model instead of focusing just on pinpointing genetic risk factors. The researchers were able to pick from all of the cases of illness within a population-based registry."

Last month, Medical News Today reported on a study that suggested exposure to pesticides during pregnancy increases risk of the child developing autism.

Written by David McNamee

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Simulated human heart used to test drugs' effects

Heart-related side effects of drugs are often only exposed once the drug is used on patients in clinical trials, at which point it is too late. But a scientist in the UK has spent 10 years developing a breakthrough new way to safely test a drug's cardiovascular effects without having to use human or animal trials - by using samples of beating heart tissue.

Dr. Helen Maddock, from the Centre for Applied Biological and Exercise Sciences at Coventry University, is an expert in cardiovascular physiology and pharmacology. She believes her new technique could improve the quality of treatment and save hundreds of patients' lives.

It works by using an in vitro technique - meaning "in glass," as it is carried out in a lab environment rather than in a living organism. Dr. Maddock uses a sample of heart tissue attached to a rig that enables the muscle to lengthen and shorten while being stimulated by an electrical impulse.

This action imitates the biomechanical performance of cardiac muscle, she explains.

Next, scientists can add trial drugs to the tissue in order to conclude whether or not they have a negative effect on the contraction of the muscles in the heart. Previously, researchers could only perform such a test on living animals, often with inconclusive results.

Because a major reason for why many medical treatments fail is negative effects of the drugs on the cardiovascular system, Dr. Maddock's technique could revolutionize the way drugs are tested before they even reach animal or human trials.

'Potential to shave years off development of successful drugs'

Her technique, called a "simulated" cardiovascular system and also known as a work-loop assay, is the most realistic heart muscle dynamic model in the world at present, one that creates the possibility of determining the negative effects of certain drugs early and without great cost.

In addition to saving lives, it could expedite development of drug treatments that work without major cardiovascular side effects.

"I'm delighted that our research is at a stage where we can confidently say the work-loop assay we've created is the world's only clinically relevant in vitro human model of cardiac contractility," says Dr. Maddock. "It has the potential to shave years off the development of successful drugs for a range of treatments."

To implement her technique in the pharma industry, she formed a spin-out company from Coventry University called InoCardia Ltd, which has already received a £250,000 ($427,000) investment from Mercia Fund Management, a UK-based technology firm.

Dr. Maddock adds:

"Both the pharma industry and regulators recognize that existing methods of assessing the contractility of the heart are fraught with problems, so we're incredibly excited to be able to introduce a new way to accurately determine the safety of drugs in respect of the heart without the need to test on humans or animals."

She and her company are currently in discussions with a multinational biopharmaceutical company regarding applying her assay in industry.

Recently, Medical News Today reported on a gene transplant procedure that transforms heart cells into a biological pacemaker that regulates the heart's beating. The procedure could mean heart patients no longer need to have an implanted pacemaker, which carries certain side effects, such as infection of the leads connecting the pacemaker to the heart.

Written by Marie Ellis

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