Loading...
Chromosome 17q12-21 Variants Are Associated with Multiple Wheezing Phenotypes in Childhood.
Hallmark, Brian; Wegienka, Ganesa; Havstad, Suzanne; Billheimer, Dean; Ownby, Dennis; Mendonca, Eneida A; Gress, Lisa; Stern, Debra A; Myers, Jocelyn Biagini; Khurana Hershey, Gurjit K; Hoepner, Lori; Miller, Rachel L; Lemanske, Robert F; Jackson, Daniel J; Gold, Diane R; O'Connor, George T; Nicolae, Dan L; Gern, James E; Ober, Carole; Wright, Anne L; Martinez, Fernando D
Journal Title
American journal of respiratory and critical care medicine
Keywords
Readers/Advisors
Journal Title
Term and Year
Publication Date
Book Title
Publication Volume
203
Publication Issue
7
Publication Begin
864
Publication End
870
Number of pages
Collections
Files
Loading...
rccm.202003-0820oc.pdf
Adobe PDF, 753.9 KB
Research Projects
Organizational Units
Journal Issue
Abstract
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. 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. Data from seven U.S. birth cohorts ( = 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) ( = 1,308) and, for the first time, in African American (AA) ( = 620) children. 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. 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.
Citation
Hallmark B, Wegienka G, Havstad S, Billheimer D, Ownby D, Mendonca EA, Gress L, Stern DA, Myers JB, Khurana Hershey GK, Hoepner L, Miller RL, Lemanske RF, Jackson DJ, Gold DR, O'Connor GT, Nicolae DL, Gern JE, Ober C, Wright AL, Martinez FD. Chromosome 17q12-21 Variants Are Associated with Multiple Wheezing Phenotypes in Childhood. Am J Respir Crit Care Med. 2021 Apr 1;203(7):864-870. doi: 10.1164/rccm.202003-0820OC. PMID: 33535024; PMCID: PMC8017591.