Noncoding variation near UBE2E2 orchestrates cardiometabolic pathophenotypes through polygenic effectors.

Mechanisms underpinning signals from genome-wide association studies remain poorly understood, particularly for noncoding variation and for complex diseases such as type 2 diabetes mellitus (T2D) where pathogenic mechanisms in multiple different tissues may be disease driving. One approach is to study relevant endophenotypes, a strategy we applied to the UBE2E2 locus where noncoding single nucleotide variants (SNVs) are associated with both T2D and visceral adiposity (a pathologic endophenotype). We integrated CRISPR targeting of SNV-containing regions and unbiased CRISPR interference (CRISPRi) screening to establish candidate cis-regulatory regions, complemented by genetic loss of function in murine diet-induced obesity or ex vivo adipogenesis assays.

Evidence for ~12-h ultradian gene programs in humans.

Mice and many marine organisms exhibit ~12-h ultradian rhythms, however, direct evidence of ~12-h ultradian rhythms in humans is lacking. Here, we performed prospective, temporal transcriptome profiling of peripheral white blood cells from three healthy humans. All three participants independently exhibited robust ~12-h transcriptional rhythms in molecular programs involved in RNA and protein metabolism, with strong homology to circatidal gene programs previously identified in Cnidarian marine species.

Evidence for conservation of primordial ~12-hour ultradian gene programs in humans under free-living conditions.

While circadian rhythms are entrained to the once daily light-dark cycle of the sun, many marine organisms exhibit ~12h ultradian rhythms corresponding to the twice daily movement of the tides. Although human ancestors emerged from circatidal environment millions of years ago, direct evidence of ~12h ultradian rhythms in humans is lacking. Here, we performed prospective, temporal transcriptome profiling of peripheral white blood cells and identified robust ~12h transcriptional rhythms from three healthy participants.

Validation of the C.A.R.E. stimulus set of 640 animal pictures: Name agreement and quality ratings.

Stimulus sets are valuable tools that can facilitate the work of researchers designing experiments. Images of faces, and line drawings of objects have been developed and validated, however, pictures of animals, that do not contain backgrounds, have not been made available. Here we present image agreement and quality ratings for a set of 640 color images of animals on a transparent background, across 60 different basic categories (e.