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On 80 WGS samples, I'm dissecting SNP signatures linked to milk production in a scarcely studied animal. Post-variant calling and QC association analysis have been tricky. I'm here to tap into our collective wisdom and refine my approach. Study Snapshot:

Objective: Identify SNPs that differentiate between high (>5 L/day) and low (<5 L/day) milk producers. Data: 80 WGS samples. Methodology:

Phenotypes were normalized (high = 1, low = 0). PCs from PCA are used to correct for population stratification, with phenotype information as a covariate. Initial approach: linear models, then FDR and Bonferroni for multiple comparison correction. A significant SNP threshold was set at <1e-5, yielding four significant SNPs. Expanded to Linear Mixed Models (LMM), we found six significant SNPs at 1e-5 and 99 at 1e-4, focusing on positive associations with high milk production.

Seeking Guidance:

Feasibility: Can 80 WGS samples provide a reliable genetic signature for milk production? Methodology Recommendations: Given my data and initial results, what methodologies or modifications could improve the analysis?

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1 Answer 1

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Visualise your problem and solution.

6 SNPs is not a particularly large search space (64 possible combinations assuming a dominant or recessive model with dimorphisms, 729 if heterozygous variants are taken into account). I would graph all those haplotypes out in a heatmap (but only the ones present in your samples, so there'd be a maximum of 80 different ones) and make sure that there is a clear pattern.

If population stratification is a concern, then you should also show the PCA, with separate colouring for the different phenotypes. If the two groups have similar spread in the PCA (which would be expected for a trait that is only affected by a small number of genes), then PCA correction doesn't make sense (and may lead to false associations).

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