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On top of these, every ‘trait’ is arbitrarily defined (to some extent). So is ‘trait-specific’…

For a single locus, I agree! I even have a mug, courtesy of @roshnipatel.bsky.social, that says "TRAITS AREN'T REAL". Across loci I'm less convinced -- regardless of how one defines traits, one can talk about whether a given locus is more or less trait-specific than another.

Signal in association studies depends on effect size, γ, and variant frequency, p: signal ~ p(1-p) γ² But natural selection throws a wrench in this – variants with bigger effects will be under stronger selection, making them rarer. 2/6

If a variant experiences strong selection, with selection coefficient s then p(1-p) ~ μ/s , where μ is the mutation rate (thanks JBS Haldane!!!). We see this in the UKB! This means: signal ~ μγ²/s 3/6

But selection only cares about a variant because of how it impacts fitness-relevant traits. Under certain assumptions (see the paper!), we have that the strength of selection is the sum of effects across all fitness-relevant traits: s = Σₜ γₜ² www.biorxiv.org/content/10.1... 4/6