TY - JOUR
T1 - Heritability of respiratory infection with pseudomonas aeruginosa in cystic fibrosis
AU - Green, Deanna M.
AU - Collaco, J. Michael
AU - McDougal, Kathryn E.
AU - Naughton, Kathleen M.
AU - Blackman, Scott M.
AU - Cutting, Garry R.
N1 - Funding Information:
We acknowledge the numerous patients with CF, their families, research coordinators, and clinicians who participated in the CF Twin and Sibling Study. We thank Christopher Watson, Vishal Doshi, MBBS, Patrick Sosnay, MD (receives grant funding from the Cystic Fibrosis Foundation, including travel reimbursements), Neeraj Sharma, DVM, PhD, Terri Beaty, PhD, and Brion Maher, PhD for their thoughtful discussions on this material, and Patricia Cornwall for her administrative assistance.
PY - 2012/8
Y1 - 2012/8
N2 - Objective: To quantify the relative contribution of factors other than cystic fibrosis transmembrane conductance regulator genotype and environment on the acquisition of Pseudomonas aeruginosa (Pa) by patients with cystic fibrosis. Study design: Lung infection with Pa and mucoid Pa was assessed using a co-twin study design of 44 monozygous (MZ) and 17 dizygous (DZ) twin pairs. Two definitions were used to establish infection: first positive culture and persistent positive culture. Genetic contribution to infection (ie, heritability) was estimated based on concordance analysis, logistic regression, and age at onset of infection through comparison of intraclass correlation coefficients. Results: Concordance for persistent Pa infection was higher in MZ (0.83; 25 of 30 pairs) than DZ twins (0.45; 5 of 11 pairs), generating a heritability of 0.76. Logistic regression adjusted for age corroborated genetic control of persistent Pa infection. The correlation for age at persistent Pa infection was higher in MZ twins (0.589; 95% CI, 0.222-0.704) than in DZ twins (0.162; 95% CI, -0.352 to 0.607), generating a heritability of 0.85. Conclusion: Genetic modifiers play a significant role in the establishment and timing of persistent Pa infection in individuals with cystic fibrosis.
AB - Objective: To quantify the relative contribution of factors other than cystic fibrosis transmembrane conductance regulator genotype and environment on the acquisition of Pseudomonas aeruginosa (Pa) by patients with cystic fibrosis. Study design: Lung infection with Pa and mucoid Pa was assessed using a co-twin study design of 44 monozygous (MZ) and 17 dizygous (DZ) twin pairs. Two definitions were used to establish infection: first positive culture and persistent positive culture. Genetic contribution to infection (ie, heritability) was estimated based on concordance analysis, logistic regression, and age at onset of infection through comparison of intraclass correlation coefficients. Results: Concordance for persistent Pa infection was higher in MZ (0.83; 25 of 30 pairs) than DZ twins (0.45; 5 of 11 pairs), generating a heritability of 0.76. Logistic regression adjusted for age corroborated genetic control of persistent Pa infection. The correlation for age at persistent Pa infection was higher in MZ twins (0.589; 95% CI, 0.222-0.704) than in DZ twins (0.162; 95% CI, -0.352 to 0.607), generating a heritability of 0.85. Conclusion: Genetic modifiers play a significant role in the establishment and timing of persistent Pa infection in individuals with cystic fibrosis.
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U2 - 10.1016/j.jpeds.2012.01.042
DO - 10.1016/j.jpeds.2012.01.042
M3 - Article
C2 - 22364820
AN - SCOPUS:84864277766
SN - 0022-3476
VL - 161
SP - 290-295.e1
JO - Journal of Pediatrics
JF - Journal of Pediatrics
IS - 2
ER -