DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Chronic mucus hypersecretion. The EFO term chronic mucus hypersecretion was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: chronic mucus hypersecretion

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

AE Dijkstra, HM Boezen, M van den Berge, JM Vonk, PS Hiemstra, RG Barr, KM Burkart, A Manichaikul, TD Pottinger, EK Silverman, MH Cho, JD Crapo, TH Beaty, P Bakke, A Gulsvik, DA Lomas, Y Bossé, DC Nickle, PD Paré, HJ de Koning, JW Lammers, P Zanen, J Smolonska, C Wijmenga, CA Brandsma, HJ Groen, DS Postma

TITLE:

Dissecting the genetics of chronic mucus hypersecretion in smokers with and without COPD.

JOURNAL:

The European respiratory journal Jan 2015, Vol 45, pp. 60-75

ABSTRACT:

Smoking is a notorious risk factor for chronic mucus hypersecretion (CMH). CMH frequently occurs in chronic obstructive pulmonary disease (COPD). The question arises whether the same single-nucleotide polymorphisms (SNPs) are related to CMH in smokers with and without COPD. We performed two genome-wide association studies of CMH under an additive genetic model in male heavy smokers (≥20 pack-years) with COPD (n=849, 39.9% CMH) and without COPD (n=1348, 25.4% CMH), followed by replication and meta-analysis in comparable populations, and assessment of the functional relevance of significantly associated SNPs. Genome-wide association analysis of CMH in COPD and non-COPD subjects yielded no genome-wide significance after replication. In COPD, our top SNP (rs10461985, p=5.43×10(-5)) was located in the GDNF-AS1 gene that is functionally associated with the GDNF gene. Expression of GDNF in bronchial biopsies of COPD patients was significantly associated with CMH (p=0.007). In non-COPD subjects, four SNPs had a p-value <10(-5) in the meta-analysis, including a SNP (rs4863687) in the MAML3 gene, the T-allele showing modest association with CMH (p=7.57×10(-6), OR 1.48) and with significantly increased MAML3 expression in lung tissue (p=2.59×10(-12)). Our data suggest the potential for differential genetic backgrounds of CMH in individuals with and without COPD. PUBMED: 25234806
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