Chromosome 17q12-21 Variants Are Associated with Multiple Wheezing Phenotypes in Childhood
Brian Hallmark, Ganesa Wegienka, Suzanne Havstad, Dean Billheimer, Dennis R. Ownby, Eneida A. Mendonça, Lisa Gress, Debra A. Stern, Jocelyn Biagini Myers, Gurjit K. Khurana Hershey, Lori Hoepner, Rachel L. Miller, Robert F. Lemanske, Daniel Jackson, Diane R. Gold, George O'connor, Dan L. Nicolae, James E. Gern, Carole Ober, Anne L. Wright, Fernando D. Martínez
Abstract
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.