Our current understanding is that a correctly implemented sib-study should be immune to population structure. As noted in the discussion, we have no specific insight into the technical or biological differences that could underlie this result.
Still trying to wrap my head around how the within family association analysis is so affected by population stratification… https://www.biorxiv.org/content/early/2018/06/25/354951 …pic.twitter.com/jeOsuO3KPt
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It is easier for me to imagine that causal variants correlated w/ latitude in R15-sibs are the result of a North-South GxE that doesn't exist in Britain than that R15-sibs is affected by population structure.
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It’s easier for me to imagine there was a bug in the R15-sib analysis.
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I think this is the main discrepancy to be explained. It's hard to imagine what kind of bug could generate this sort of systematic relationship! (P.S. I would rather see a 3D plot of R15 and UKB effect sizes on separate axes against [GBR-TSI]freq; better to see any clustering).pic.twitter.com/9wDxrj1oUk
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You’d see this relationship if the effect of b_k is improperly estimated.pic.twitter.com/vOUWLkJUz4
End of conversation
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