Use of a modeling framework to evaluate the effect of a modifier gene (MBL2) on variation in cystic fibrosis

Kathryn E. McDougal, Deanna M. Green, Lori L. Vanscoy, M. Daniele Fallin, Michael Grow, Suzanne Cheng, Scott M. Blackman, J. Michael Collaco, Lindsay B. Henderson, Kathleen Naughton, Garry R. Cutting

Research output: Contribution to journalArticlepeer-review

Abstract

Variants in mannose-binding lectin (MBL2; protein MBL) have shown association with different aspects (eg, lung function, infection, survival) of cystic fibrosis (CF) in some studies but not others. Inconsistent results may be due to confounding among disease variables that were not fully accounted for in each study. To account for these relationships, we derived a modeling framework incorporating CFTR genotype, age, Pseudomonas aeruginosa (Pa) infection, and lung function from 788 patients in the US CF Twin and Sibling Study. This framework was then used to identify confounding variables when testing the effect of MBL2 variation on specific CF traits. MBL2 genotypes corresponding to low levels of MBL associated with Pa infection 1.94 years earlier than did MBL2 genotypes corresponding to high levels of MBL (P=0.0034). In addition, Pa-infected patients with MBL2 genotypes corresponding to low levels of MBL underwent conversion to mucoid Pa 2.72 years earlier than did patients with genotypes corresponding to high levels of MBL (P=0.0003). MBL2 was not associated with the time to transition from infection to conversion or with lung function. Thus, use of a modeling framework that identified confounding among disease variables revealed that variation in MBL2 associates with age at infection with Pa and age at conversion to mucoid Pa in CF.

Original languageEnglish (US)
Pages (from-to)680-684
Number of pages5
JournalEuropean Journal of Human Genetics
Volume18
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • Confounding
  • Immunity
  • Infection

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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