11:58pm Sunday 26 January 2020

SickKids-led study identifies multiple genes linked to differences in cystic fibrosis

Researchers have long been puzzled as to how individuals who carry the same CFTR mutations can experience such different courses of disease. Patients with CF are affected in multiple organs such as the lungs, pancreas and liver, to varying degrees.  

An international team led by The Hospital for Sick Children (SickKids) and the University for Toronto (U of T) has found a potential answer to this puzzle. The team has discovered multiple genes associated with meconium ileus, a severe intestinal obstruction present at birth in 15 per cent of patients with CF. The study is published online in Nature Genetics.

“Because meconium ileus is inherited, present at birth, and subject to limited environmental influence, it provides an ideal focus for identifying other contributors beyond CFTR that could result in differences in CF disease,” says the study’s principal investigator Dr. Lisa Strug, a Scientist in Child Health Evaluative Sciences at SickKids Research Institute and an Assistant Professor at the Dalla Lana School of Public Health at the University of Toronto.

The team studied the genomes of almost 4,000 CF patients from the International Consortium in Gene Modifiers of CF. They developed and implemented a novel statistical technique that incorporated information about the causal CFTR gene to identify other CF-related genes. Multiple genes associated with developing meconium ileus were identified as a consequence, and some of these genes are anticipated to influence disease in other CF-affected organs.  

“This work highlights the benefit of integrating statistical methodology with other disciplines in scientific studies,” says Dr. Lei Sun, an Associate Professor at the Dalla Lana School of Public Health and the Department of Statistics at U of T. Sun shares first-authorship on the study with Dr. Johanna Rommens, a Senior Scientist in Genetics & Genome Biology at SickKids Research Institute and a Professor of Molecular Genetics at U of T.

“In cystic fibrosis, CFTR does not function normally, which causes disease,” says Strug.  “Identifying other genes that influence the degree of organ-specific CF disease suggests the possibility of personalized approaches to treatment for individuals with CF, as well as novel therapeutic targets.”

“We are proud to support Dr. Strug’s important cystic fibrosis research, allowing us to advance treatment, and bring us closer to finding a cure,” said Maureen Adamson, Chief Executive Officer at Cystic Fibrosis Canada. “Cystic Fibrosis Canada plays a leading role in the worldwide race for a cure. In 2012/13, we will invest more than $7.5 million in innovative research and clinical care for Canadians living with this devastating disease and will fund 51 research projects, six targeted programs and partnerships, and 47 fellows and students.”

The study was supported by the Canadian Institutes of Health Research, Cystic Fibrosis Canada, the Cystic Fibrosis Foundation, the University of Toronto McLaughlin Centre, Genome Canada, the Ontario Research Fund, the National Institutes of Health, SickKids Foundation, and the Natural Sciences and Engineering Research Council of Canada.

About The Hospital for Sick Children

The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally.  Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision for Healthier Children. A Better World. For more information, please visit www.sickkids.ca.

About the University of Toronto

Established in 1827, the University of Toronto has assembled one of the strongest research and teaching faculties in North America, presenting top students at all levels with an intellectual environment unmatched in breadth and depth on any other Canadian campus. U of T faculty co-author more research articles than their colleagues at any university in the US or Canada other than Harvard. As a measure of impact, U of T consistently ranks alongside the top five U.S. universities whose discoveries are most often cited by other researchers around the world.  The U of T faculty are also widely recognized for their teaching strengths and commitment to graduate supervision. www.utoronto.ca.          

For more information, please contact:

Suzanne Gold
The Hospital for Sick Children
416-813-7654, ext. 2059

Jim Oldfield
University of Toronto Faculty of Medicine

Share on:

MORE FROM Genetics and Birth Defects

Health news