Watershed moment for COPD research

A genome-wide association study of almost 50,000 people representing the extremes of  lung function has helped uncover 68 high priority genes as targets for future COPD drug development.

The findings, published in Nature Genetics, also demonstrated the magnitude of the combined effect of genes on COPD susceptibility – with a 3.7 fold difference in COPD risk between individuals with the highest genetic risk score and the lowest.

Co-author and respiratory physician Professor Alan James, from the University of Western Australia and chair of the Busselton Population Medical Research Institute, said the comprehensive international study was a watershed in COPD research.

“This study emphasises the importance of genetics in lung function, and while it certainly creates many more questions, it also shows us the way forward. In the future we will need to look at people’s genetic signatures and specify drug treatment based on their combination of genes,” he told the limbic in an interview.

Some of the high priority genes identified in the study such as CHRM3 are known for encoding targets for drugs already approved for the treatment of asthma or COPD.

“For example, we use ipratropium to block the muscarinic acetylcholine receptor. As a secondary bronchodilator, it improves lung function and quality of life for patients with some forms of COPD.”

“However it may be that genes like CHRM3 have roles in other ways yet to be determined,” Professor James said.

He said other high priority genes identified in the study were involved in elastic recoil of the lungs, early lung development, epigenetic regulation pathways and inflammation.

“Lung function is a product of whole-of-life exposures. Lung function later in life is determined by how a foetus responds to maternal smoking as early as 12 weeks in utero, how an infant responds to a viral infection in their first six months of life, growth and expansion of the lungs during childhood and adolescence, and inflammation in adulthood.”

He said it was likely the genes that affect lung function at a particular time point in life were different to those that affect declining lung function.

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