Richard B Parad1, Abigail B Winston2, Leslie A Kalish3, Munish Gupta4, Ivana Thompson5, Yvonne Sheldon2, Joann Morey2, Linda J Van Marter6. 1. Brigham and Women's Hospital, Boston, MA; Boston Children's Hospital, Boston, MA; Harvard Medical School, Boston, MA. Electronic address: rparad@bwh.harvard.edu. 2. Brigham and Women's Hospital, Boston, MA. 3. Boston Children's Hospital, Boston, MA; Harvard Medical School, Boston, MA. 4. Boston Children's Hospital, Boston, MA; Harvard Medical School, Boston, MA; Beth Israel Deaconess Medical Center, Boston, MA. 5. Vanderbilt University Medical Center, Nashville, TN. 6. Brigham and Women's Hospital, Boston, MA; Boston Children's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
Abstract
OBJECTIVE: To assess heritable contributions to bronchopulmonary dysplasia (BPD) risk in a twin cohort restricted to gestational age at birth <29 weeks. STUDY DESIGN: A total of 250 twin pairs (192 dichorionic, 58 monochorionic) born <29 weeks gestational age with known BPD status were identified. Three statistical methods applicable to twin cohorts (χ2 test, intraclass correlations [ICCs], and ACE modeling [additive genetic or A, common environmental or C, and unique environmental or E components]) were applied. Heritability was estimated as percent variability from A. Identical methods were applied to a subcohort defined by zygosity and to an independent validation cohort. RESULTS: χ2 analyses comparing whether neither, 1, or both of monochorionic (23, 19, 16) and dichorionic (88, 56, 48) twin pairs developed BPD revealed no difference. Although there was similarity in BPD outcome within both monochorionic and dichorionic twin pairs by ICC (monochorionic ICC = 0.34, 95% CI [0.08, 0.55]; dichorionic ICC = 0.39, 95% CI [0.25, 0.51]), monochorionic twins were not more likely than dichorionic twins to have the same outcome (P = .70). ACE modeling revealed no contribution of heritability to BPD risk (% A = 0.0%, 95% CI [0.0%, 43.1%]). Validation and zygosity based cohort results were similar. CONCLUSIONS: Our analysis suggests that heritability is not a major contributor to BPD risk in preterm infants <29 weeks gestational age.
OBJECTIVE: To assess heritable contributions to bronchopulmonary dysplasia (BPD) risk in a twin cohort restricted to gestational age at birth <29 weeks. STUDY DESIGN: A total of 250 twin pairs (192 dichorionic, 58 monochorionic) born <29 weeks gestational age with known BPD status were identified. Three statistical methods applicable to twin cohorts (χ2 test, intraclass correlations [ICCs], and ACE modeling [additive genetic or A, common environmental or C, and unique environmental or E components]) were applied. Heritability was estimated as percent variability from A. Identical methods were applied to a subcohort defined by zygosity and to an independent validation cohort. RESULTS: χ2 analyses comparing whether neither, 1, or both of monochorionic (23, 19, 16) and dichorionic (88, 56, 48) twin pairs developed BPD revealed no difference. Although there was similarity in BPD outcome within both monochorionic and dichorionic twin pairs by ICC (monochorionic ICC = 0.34, 95% CI [0.08, 0.55]; dichorionic ICC = 0.39, 95% CI [0.25, 0.51]), monochorionic twins were not more likely than dichorionic twins to have the same outcome (P = .70). ACE modeling revealed no contribution of heritability to BPD risk (% A = 0.0%, 95% CI [0.0%, 43.1%]). Validation and zygosity based cohort results were similar. CONCLUSIONS: Our analysis suggests that heritability is not a major contributor to BPD risk in preterm infants <29 weeks gestational age.
Authors: Bernard Thébaud; Kara N Goss; Matthew Laughon; Jeffrey A Whitsett; Steven H Abman; Robin H Steinhorn; Judy L Aschner; Peter G Davis; Sharon A McGrath-Morrow; Roger F Soll; Alan H Jobe Journal: Nat Rev Dis Primers Date: 2019-11-14 Impact factor: 52.329
Authors: Richard B Parad; Janis L Breeze; Norma Terrin; Lynette K Rogers; Carolyn M Salafia; Anne Greenough; Jonathan M Davis Journal: Pediatr Pulmonol Date: 2021-08-26