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Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma.

Publication ,  Conference
Kachroo, P; Hecker, J; Chawes, BL; Ahluwalia, TS; Cho, MH; Qiao, D; Kelly, RS; Chu, SH; Virkud, YV; Huang, M; Barnes, KC; Burchard, EG; Hu, D ...
Published in: Chest
December 2019

BACKGROUND: Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma. METHODS: WGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician's diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes. RESULTS: A genome-wide significant association was identified between baseline FEV1/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10-8 in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10-6). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV1 (P = 3.3 × 10-3), postbronchodilator (PB) FEV1 (7.3 × 10-3), and PB FEV1/FVC ratio (P = 2.7 × 10-3). The identified baseline FEV1/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR. CONCLUSIONS: These findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

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Published In

Chest

DOI

EISSN

1931-3543

Publication Date

December 2019

Volume

156

Issue

6

Start / End Page

1068 / 1079

Location

United States

Related Subject Headings

  • Young Adult
  • Whole Genome Sequencing
  • Vital Capacity
  • Respiratory System
  • Respiratory Physiological Phenomena
  • Middle Aged
  • Male
  • Interferon Regulatory Factors
  • Humans
  • Forced Expiratory Volume
 

Citation

APA
Chicago
ICMJE
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Kachroo, P., Hecker, J., Chawes, B. L., Ahluwalia, T. S., Cho, M. H., Qiao, D., … National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, . (2019). Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma. In Chest (Vol. 156, pp. 1068–1079). United States. https://doi.org/10.1016/j.chest.2019.08.2202
Kachroo, Priyadarshini, Julian Hecker, Bo L. Chawes, Tarunveer S. Ahluwalia, Michael H. Cho, Dandi Qiao, Rachel S. Kelly, et al. “Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma.” In Chest, 156:1068–79, 2019. https://doi.org/10.1016/j.chest.2019.08.2202.
Kachroo P, Hecker J, Chawes BL, Ahluwalia TS, Cho MH, Qiao D, et al. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma. In: Chest. 2019. p. 1068–79.
Kachroo, Priyadarshini, et al. “Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma.Chest, vol. 156, no. 6, 2019, pp. 1068–79. Pubmed, doi:10.1016/j.chest.2019.08.2202.
Kachroo P, Hecker J, Chawes BL, Ahluwalia TS, Cho MH, Qiao D, Kelly RS, Chu SH, Virkud YV, Huang M, Barnes KC, Burchard EG, Eng C, Hu D, Celedón JC, Daya M, Levin AM, Gui H, Williams LK, Forno E, Mak ACY, Avila L, Soto-Quiros ME, Cloutier MM, Acosta-Pérez E, Canino G, Bønnelykke K, Bisgaard H, Raby BA, Lange C, Weiss ST, Lasky-Su JA, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma. Chest. 2019. p. 1068–1079.

Published In

Chest

DOI

EISSN

1931-3543

Publication Date

December 2019

Volume

156

Issue

6

Start / End Page

1068 / 1079

Location

United States

Related Subject Headings

  • Young Adult
  • Whole Genome Sequencing
  • Vital Capacity
  • Respiratory System
  • Respiratory Physiological Phenomena
  • Middle Aged
  • Male
  • Interferon Regulatory Factors
  • Humans
  • Forced Expiratory Volume