Chromosome 17q12-21 Variants Are Associated with Multiple Wheezing Phenotypes in Childhood

被引：37

作者：

Hallmark, Brian ^{[1
,2
]}

Wegienka, Ganesa ^{[5
]}

Havstad, Suzanne ^{[5
]}

Billheimer, Dean ^{[2
,3
]}

Ownby, Dennis ^{[5
]}

Mendonca, Eneida A. ^{[6
,7
,8
]}

Gress, Lisa ^{[9
]}

Stern, Debra A. ^{[1
]}

Myers, Jocelyn Biagini ^{[10
]}

Hershey, Gurjit K. Khurana ^{[10
]}

Hoepner, Lori ^{[11
,12
]}

Miller, Rachel L. ^{[13
]}

Lemanske, Robert F. ^{[9
]}

Jackson, Daniel J. ^{[9
]}

Gold, Diane R. ^{[14
,15
]}

O'Connor, George T. ^{[16
]}

Nicolae, Dan L. ^{[17
,18
]}

Gern, James E. ^{[9
]}

Ober, Carole ^{[17
]}

Wright, Anne L. ^{[1
,4
]}

Martinez, Fernando D. ^{[1
,4
]}

机构：

[1] Univ Arizona, Asthma & Airway Dis Res Ctr, Tucson, AZ 85724 USA

[2] Univ Arizona, Inst BIO5, Tucson, AZ 85724 USA

[3] Univ Arizona, Coll Publ Hlth, Tucson, AZ 85724 USA

[4] Univ Arizona, Dept Pediat, Tucson, AZ 85724 USA

[5] Henry Ford Hosp & Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA

[6] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA

[7] Indiana Univ, Dept Pediat, Indianapolis, IN USA

[8] Indiana Univ, Regenstrief Inst, Indianapolis, IN USA

[9] Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Madison, WI USA

[10] Univ Cincinnati, Coll Med, Dept Pediat, Div Asthma Res,Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA

[11] Downstate Hlth Sci Univ, SUNY, Dept Environm & Occupat Hlth Sci, Sch Publ Hlth, Brooklyn, NY USA

[12] Columbia Univ, Columbia Ctr Childrens Environm Hlth, Mailman Sch Publ Hlth, New York, NY USA

[13] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA

[14] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

[15] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA

[16] Boston Univ, Dept Pediat, Boston, MA USA

[17] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[18] Univ Chicago, Dept Stat, Chicago, IL 60637 USA

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2021年 / 203卷 / 07期

关键词：

latent class analysis; genetics; 17q12-21; wheeze; asthma; 1ST; 6; YEARS; RISK-FACTORS; ASTHMA; 17Q21; INFECTIONS; EXPRESSION; CHILDREN; ILLNESS; BIRTH; GSDMB;

D O I：

10.1164/rccm.202003-0820OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

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 virusescommon to all wheezing children. Which children will have their symptoms remit or reoccur during childhood may be independent of the influence of rs2305480.

引用

页码：864 / 870

页数：7