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I'm excited to share that our work studying gene dosage response curves (GDRCs) is now out in Cell Genomics (@cellpress.bsky.social). www.cell.com/cell-genomic... [1/n]

cell.comBuffering of gene dosage response curves for human complex traitsMilind et al. explore why loss-of-function variants and duplications tend to have average effects in the same direction on 94 complex traits. Using gene dosage response curves (GDRCs), they gather evi...

Nikhil Milind

@nikhilmilind.dev

With amazing collaborators @courtsmithrun.bsky.social, @huishengzhu.bsky.social, @tamigj.bsky.social, and my mentors @jeffspence.github.io and @jkpritch.bsky.social. [2/n]

26/5/26, 11:59 pm0 reposts2 likes

Nikhil Milind

@nikhilmilind.dev

26 May

We observed that the average effect of gene deletions (LoF) and gene duplications was positively correlated across traits. We use the GDRC to conceptualize what types of gene dosage architectures may explain this pattern. [3/n]

Nikhil Milind

@nikhilmilind.dev

26 May

We find that this pattern is explained by trait buffering, which is the propensity for GDRCs to be buffered against modifying the trait in one particular direction over the other. [4/n]

Nikhil Milind

@nikhilmilind.dev

26 May

We propose a simple model of an upstream "dysregulation" phenotype that may explain why GDRCs organize themselves in this manner. [5/n]

Nikhil Milind

@nikhilmilind.dev

27 May

I think GDRCs are a conceptually pleasing way to tie together various estimates of gene effect that are used in the field (e.g., burden tests, TWAS). [6/n]