Thread by @Riudecanyenc

Our new study on genetic determinants of dietary intake is out in @NatureHumBehav

Paper: nature.com/articles/s4156…

Press release: massgeneral.org/news/press-rel…

Summary stats will be available soon at @AMP_CMDKP

A short summary below:

Diet is an extremely complex exposure. In addition to measurement error, noise, correlation with other traits, reverse causation, or variation across life course, diet is based on substitutions. That is, a higher intake of A necessarily implies lower intakes from B and C.

To accommodate the substitution nature of diet, we used multivariate GWAS to factor the correlation between dietary carbohydrate, fat, and protein in 282,271 participants of European ancestry from @uk_biobank and CHARGE Consortium @chargetiger

Why macronutrients?

A) Genetic variation for macronutrient intake has the potential to highlight biological mechanisms related to central nervous system nutrient sensing.

B) Macronutrient intake is less confounded by social, environmental or demographic factors than foods.

We identified 26 distinct genomic loci associated with overall variation in dietary intake. Among them, 14 were not previously reported by @fleurmeddens in the largest GWAS for macronutrient intake to date nature.com/articles/s4138….

What did we find:

a) Diet signals are enriched for genes expressed in several #brain regions including the cerebellum or frontal cortex.

b) scRNA-seq analysis in 119 whole-body cell types showed that diet signals are enriched for genes exclusively expressed in #neurons

c) GABAergic, dopaminergic, and glutamatergic neurons distributed across several brain regions are enriched for diet signals.

For example, we identified a highly specialized type of dopamine neuron expressing prolactin receptor gene enriched for genes associated with fat intake

d) We used a clustering algorithm to group genetic variants based on biological and phenotypic similarities. We identified two main domains of genetic that may have distinct association with #obesity and #cardiovascular disease.

There are important limitations to this study, including the self-report of dietary intake, the predominant effect of social and environmental factors on eating behavior, reverse causation, or the inclusion of relatively healthy European descent participants.

Shoutout to all co-authors

Special shoutout to the co-first (@SarnowskiChloe & @hsdash) and senior authors (Dupuis J, Florez JC, Saxena R).

Amazing experience working with colleagues from the @Metabolcenter (@pvtodorov & @tunepers).

Big thanks to my funding sources