DOI: 10.5061/dryad.8cz8w9gxc
title: A pilot GWAS in children from the BEECH study using the H3Africa chip

description: 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
 &lt; -2) were enrolled and given nutritional therapy. Those that were
 non-responsive to therapy were designated as cases, and children with good
 growth (LAZ &gt; -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&lt;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&lt;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.
description: # 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: 1. 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:
 In summary; 1.
 BEECH_H3Africa.bed: Primary representation of genotype calls at biallelic
 variants. 2. BEECH_H3Africa.bim: Extended variant information file
 accompanying a .bed binary genotype table 3. BEECH_H3Africa.fam: Sample
 information file accompanying a .bed binary genotype table. 2.
 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: *