Today insitro announces an exciting new collaboration with insighteyehub.bsky.social at Moorfields Eye Hospital, London, through the development of a novel #AI foundation model to identify and to support #drugdiscovery. Learn more: www.businesswire.com/news/home/20...

@tkaraletsos.bsky.social, Daphne Koller, Hugues Aschard, @mendelrandom.bsky.social, @dgmacarthur.bsky.social, @codushlaine.bsky.social, and additional members of the team at @insitro.bsky.social !

Congrats to the team and our collaborators! @zmccaw.bsky.social, Rounak Dey, Hari Somineni, David Amar, @smukherjee89.bsky.social, Kaitlin Sandor, ...

In summary, associations with ratio traits are not specific to the ratio per se. Practitioners considering GWAS on ratios should examine the motivation for forming the ratio. We provide guidance on how to approach GWAS of related pairs of traits in light of analysis objectives.

In the case where the denominator is heritable and collider bias is a concern, we propose additionally adjusting for a leave-one-chromosome-out polygenic score (LOCO-PGS) of the denominator, which we show corrects for collider bias due to genetic background.

Instead of a ratio model, we propose a model that adjusts for the denominator as a covariate, e.g. to detect the genetic effect on weight while holding height constant. Loci from weight adjusted for height GWAS were enriched for adiposity-related signals more so than loci from the BMI GWAS.

Examining ratio traits commonly used in clinical practice and genetic association testing, such as waist-to-hip ratio and albumin-to-creatinine ratio, we find that loci detected by the ratio model are enriched for denominator signals.

Top “hits” from ratio trait GWASs can be driven entirely by the denominator. This means, for example, that attempts to find genes associated with BMI may return genes associated entirely with height (only), and not weight.

With high-dimensional omics and imaging data, there is a temptation to test all pairs of ratios to increase power. We caution against this approach; GWAS on ratio traits may increase the number of significant associations, but it does so by conflating signals for the numerator and denominator.

Excited to share a new paper from @insitro.bsky.social (first author @zmccaw.bsky.social ) in @hggadvances.bsky.social vances.bsky.social on scrutinizing the practice of using a ratio trait (numerator / denominator) for GWAS.

www.cell.com/hgg-advances...