Back

Genome-wide association study of human pineal gland volume as proxy for melatonin secretion

xu, p.; Imtiaz, M. A.; Rusman, D.; estrada, s.; Reuter, M.; Breteler, M. M. B.; Aziz, N. A.

2025-03-11 genetic and genomic medicine
10.1101/2025.03.10.25323654 medRxiv
Show abstract

The pineal gland is the primary source of melatonin synthesis and secretion. Reduced pineal gland volume results in lower melatonin levels and has been linked to sleep impairment, as well as many (age-related) metabolic and neurodegenerative disorders. However, its genetic architecture remains unknown. Using brain imaging and genotype data from the UK Biobank (N=38,254) and Rhineland Study (N=5,286), we conducted the first genome-wide association study (GWAS) of pineal gland volume, demonstrating 19% heritability and identifying 34 genome-wide significant loci, with highly concordant results between the two independent cohorts. Gene mapping and functional annotation highlighted multiple genes and pathways involved in numerous traits including sleep, metabolism, neurodevelopment and neurodegeneration. Mendelian randomization indicated a causal relationship between pineal gland volume and daytime napping. Our findings elucidate the genetic architecture of pineal gland volume and identify candidate genes and molecular pathways that may affect sleep/circadian rhythm, metabolism, neuronal development and brain health.

Matching journals

The top 3 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.