TY - JOUR T1 - Variation in MSRA Modifies Risk of Neonatal Intestinal Obstruction in Cystic Fibrosis A1 - Henderson, Lindsay B. A1 - Doshi, Vishal K. A1 - Blackman, Scott M. A1 - Naughton, Kathleen M. A1 - Pace, Rhonda G. A1 - Moskovitz, Jackob A1 - Knowles, Michael R. A1 - Durie, Peter R. A1 - Drumm, Mitchell L. A1 - Cutting, Garry R. Y1 - 2012/03/15 N2 - Author Summary Cystic fibrosis (CF) is a monogenic disease with considerable phenotypic variability. About 15% of newborns with CF suffer from an intestinal obstruction called meconium ileus (MI), and studies in CF twins have shown that modifier genes play a substantial role in the development of this complication. We used a family-based study design to enrich for genetic modifiers of MI and found that variations in the MSRA gene, represented by combinations of SNPs, or haplotypes, were protective against this manifestation of CF. We investigated association between one of the MSRA haplotypes and MI in an independent sample of CF patients and showed that it had a similar protective effect. Furthermore, CF mice lacking Msra expression had lower mortality due to intestinal obstruction at the time of transitioning to solid food and lived longer than CF mice with normal Msra, thus supporting the protective effect of the haplotype we observed in human CF subjects. The identification of modifiers of MI such as MSRA offers new insight into the mechanism of this life-threatening complication of CF. JF - PLOS Genetics JA - PLOS Genetics VL - 8 IS - 3 UR - https://doi.org/10.1371/journal.pgen.1002580 SP - e1002580 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pgen.1002580 ER -