Brian Hallmark1,2, Ganesa Wegienka3, Suzanne Havstad3, Dean Billheimer2,4, Dennis Ownby3, Eneida A Mendonca5,6,7, Lisa Gress8, Debra A Stern1, Jocelyn Biagini Myers9, Gurjit K Khurana Hershey9, Lori Hoepner10,11, Rachel L Miller12, Robert F Lemanske8, Daniel J Jackson8, Diane R Gold13,14, George T O'Connor15, Dan L Nicolae16,17, James E Gern8, Carole Ober16, Anne L Wright1,18, Fernando D Martinez1,18. 1. Asthma and Airway Disease Research Center. 2. BIO5 Institute. 3. Department of Public Health Sciences, Henry Ford Hospital and Health System, Detroit, Michigan. 4. College of Public Health, and. 5. Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin. 6. Department of Pediatrics and. 7. Regenstrief Institute, Indiana University, Indianapolis, Indiana. 8. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. 9. Division of Asthma Research, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio. 10. Department of Environmental and Occupational Health Sciences, Downstate Health Sciences University School of Public Health, State University of New York, Brooklyn, New York. 11. Columbia Center for Children's Environmental Health, Mailman School of Public Health, Columbia University, New York, New York. 12. Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. 13. The Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 14. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 15. Department of Pediatrics, Boston University, Boston, Massachusetts; and. 16. Department of Human Genetics and. 17. Department of Statistics, University of Chicago, Chicago, Illinois. 18. Department of Pediatrics, University of Arizona, Tucson, Arizona.
Abstract
Rationale: Birth cohort studies have identified several temporal patterns of wheezing, only some of which are associated with asthma. Whether 17q12-21 genetic variants, which are closely associated with asthma, are also associated with childhood wheezing phenotypes remains poorly explored. Objectives: To determine whether wheezing phenotypes, defined by latent class analysis (LCA), are associated with nine 17q12-21 SNPs and if so, whether these relationships differ by race/ancestry. Methods: Data from seven U.S. birth cohorts (n = 3,786) from the CREW (Children's Respiratory Research and Environment Workgroup) were harmonized to represent whether subjects wheezed in each year of life from birth until age 11 years. LCA was then performed to identify wheeze phenotypes. Genetic associations between SNPs and wheeze phenotypes were assessed separately in European American (EA) (n = 1,308) and, for the first time, in African American (AA) (n = 620) children.Measurements and Main Results: The LCA best supported four latent classes of wheeze: infrequent, transient, late-onset, and persistent. Odds of belonging to any of the three wheezing classes (vs. infrequent) increased with the risk alleles for multiple SNPs in EA children. Only one SNP, rs2305480, showed increased odds of belonging to any wheezing class in both AA and EA children.Conclusions: These results indicate that 17q12-21 is a "wheezing locus," and this association may reflect an early life susceptibility to respiratory viruses common to all wheezing children. Which children will have their symptoms remit or reoccur during childhood may be independent of the influence of rs2305480.
Rationale: Birth cohort studies have identified several temporal patterns of wheezing, only some of which are associated with asthma. Whether 17q12-21 genetic variants, which are closely associated with asthma, are also associated with childhood wheezing phenotypes remains poorly explored. Objectives: To determine whether wheezing phenotypes, defined by latent class analysis (LCA), are associated with nine 17q12-21 SNPs and if so, whether these relationships differ by race/ancestry. Methods: Data from seven U.S. birth cohorts (n = 3,786) from the CREW (Children's Respiratory Research and Environment Workgroup) were harmonized to represent whether subjects wheezed in each year of life from birth until age 11 years. LCA was then performed to identify wheeze phenotypes. Genetic associations between SNPs and wheeze phenotypes were assessed separately in European American (EA) (n = 1,308) and, for the first time, in African American (AA) (n = 620) children.Measurements and Main Results: The LCA best supported four latent classes of wheeze: infrequent, transient, late-onset, and persistent. Odds of belonging to any of the three wheezing classes (vs. infrequent) increased with the risk alleles for multiple SNPs in EA children. Only one SNP, rs2305480, showed increased odds of belonging to any wheezing class in both AA and EA children.Conclusions: These results indicate that 17q12-21 is a "wheezing locus," and this association may reflect an early life susceptibility to respiratory viruses common to all wheezing children. Which children will have their symptoms remit or reoccur during childhood may be independent of the influence of rs2305480.
Entities:
Keywords:
17q12-21; asthma; genetics; latent class analysis; wheeze
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