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 Congenital left-sided heart lesions. The EFO term congenital left-sided heart lesions 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: congenital left-sided heart lesions

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

NA Hanchard, S Swaminathan, K Bucasas, D Furthner, S Fernbach, MS Azamian, X Wang, M Lewin, JA Towbin, LC D'Alessandro, SA Morris, W Dreyer, S Denfield, NA Ayres, WJ Franklin, H Justino, MR Lantin-Hermoso, EC Ocampo, AB Santos, D Parekh, D Moodie, A Jeewa, E Lawrence, HD Allen, DJ Penny, CD Fraser, JR Lupski, M Popoola, L Wadhwa, JD Brook, FA Bu'Lock, S Bhattacharya, SR Lalani, GA Zender, SM Fitzgerald-Butt, J Bowman, D Corsmeier, P White, K Lecerf, G Zapata, P Hernandez, JA Goodship, V Garg, BD Keavney, SM Leal, HJ Cordell, JW Belmont, KL McBride

TITLE:

A genome-wide association study of congenital cardiovascular left-sided lesions shows association with a locus on chromosome 20.

JOURNAL:

Human molecular genetics Jun 2016, Vol 25, pp. 2331-2341

ABSTRACT:

Congenital heart defects involving left-sided lesions (LSLs) are relatively common birth defects with substantial morbidity and mortality. Previous studies have suggested a high heritability with a complex genetic architecture, such that only a few LSL loci have been identified. We performed a genome-wide case-control association study to address the role of common variants using a discovery cohort of 778 cases and 2756 controls. We identified a genome-wide significant association mapping to a 200 kb region on chromosome 20q11 [P= 1.72 × 10(-8) for rs3746446; imputed Single Nucleotide Polymorphism (SNP) rs6088703 P= 3.01 × 10(-9), odds ratio (OR)= 1.6 for both]. This result was supported by transmission disequilibrium analyses using a subset of 541 case families (lowest P in region= 4.51 × 10(-5), OR= 1.5). Replication in a cohort of 367 LSL cases and 5159 controls showed nominal association (P= 0.03 for rs3746446) resulting in P= 9.49 × 10(-9) for rs3746446 upon meta-analysis of the combined cohorts. In addition, a group of seven SNPs on chromosome 1q21.3 met threshold for suggestive association (lowest P= 9.35 × 10(-7) for rs12045807). Both regions include genes involved in cardiac development-MYH7B/miR499A on chromosome 20 and CTSK, CTSS and ARNT on chromosome 1. Genome-wide heritability analysis using case-control genotyped SNPs suggested that the mean heritability of LSLs attributable to common variants is moderately high ([Formula: see text] range= 0.26-0.34) and consistent with previous assertions. These results provide evidence for the role of common variation in LSLs, proffer new genes as potential biological candidates, and give further insight to the complex genetic architecture of congenital heart disease. PUBMED: 26965164
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