A pilot GWAS in children from the BEECH study using the H3Africa chip
Data files
Sep 08, 2023 version files 68.83 MB
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BEECHkids_edited_pheno_casecontrol.txt
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H3Africa_BEECH_Zambia.zip
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README.md
Jan 31, 2024 version files 68.83 MB
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BEECH_CaseControl_phenotype.txt
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BEECH_H3Africa_Zambia.zip
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README.md
Abstract
Purpose: Stunting is known to be heavily influenced by environmental factors, so the genetic contribution has received little attention. Here we report an exploration of genetic influences in stunted Zambian children with environmental enteropathy.
Method: Children with stunting (LAZ < -2) were enrolled and given nutritional therapy. Those that were non-responsive to therapy were designated as cases, and children with good growth (LAZ > -1) from the same community as controls. Blood and stool samples were taken to measure biomarkers of intestinal inflammation, epithelial damage, and microbial translocation. Single nucleotide polymorphism array genotyping was carried out on saliva samples using the H3Africa consortium array.
Results: Genome wide associations were analysed in 117 cases and 41 controls. While no significant associations with stunting were observed at P<5x10-8, likely due to the small sample size, interesting associations were observed at lower thresholds. SNPs associated with stunting were in genomic regions known to modulate neuronal differentiation and fatty acid biosynthesis. SNPs associated with increased microbial translocation were associated with non-integrin membrane ECM interactions, tight junctions, hemostasis, and G-alpha signalling events. SNPs associated with increased inflammation were associated with, ECM interactions, purine metabolism, axon guidance, and cell motility. SNPs negatively associated with inflammation overlapped genes involved in semaphoring interactions. We explored the existing coeliac disease risk HLA genotypes and found present: DQ2.5 (7.5%), DQ8 (3.5%) and DQ2.2 (3.8%); however, no children were positive for coeliac antibodies. We detected HLA-DRB:1301 and HLA-C:1802 with high odds ratios and P<0.05 in stunted children compared to controls.
Conclusion: Genetic variations associated with stunting and the enteropathy underlying it, include variants associated with multiple pathways relating to gene expression, glycosylation, nerve signalling, and sensing of the nutritional and microbiological milieu.
README: A pilot GWAS in children from the BEECH study using the H3Africa chip
This is a dataset from children in the BEECH study made from genotyping data using the H3Africa Consortium Array (Illumina). Full description of laboratory procedures used to derive this data are found there: 10.1371/journal.pone.0291311
Description of the data and file structure
There are 2 file:
BEECH_H3Africa_Zambia.zip: This contains 3 files of the genotyped data for this study in PLINK format i.e. .bim, .bed and .fam files. These three files are used together to look at summary statistics and carry out association analysis with additional metadata.
Detailed description of these files can be found here: https://www.cog-genomics.org/plink/1.9/formats#bed
In summary;- BEECH_H3Africa.bed: Primary representation of genotype calls at biallelic variants.
- BEECH_H3Africa.bim: Extended variant information file accompanying a .bed binary genotype table
- BEECH_H3Africa.fam: Sample information file accompanying a .bed binary genotype table.
BEECH_CaseControl_phenotype.txt: This is an additional .txt file that explains the case-control status of each participants. This file accompanies the .fam file
Sharing/Access information
Links to other publicly accessible locations of the data:
Data was derived from the following sources: