SUMMARY Body mass results from a complex interplay between genetics and environment. The contribution of genetic variation to body mass has been extensively studied, but due to the technical limitations of platforms used for population scale studies, repetitive parts of the genome have not previously been considered. Here we applied genome-wide approaches to identify an association between adult body mass and the copy number (CN) of 45S-ribosomal DNA (rDNA). rDNA codes for the rRNA components of the ribosome and exists in hundreds of copies/cell in mammals. Inter-individual variation in rDNA CN has not previously been documented but has not been associated with a mammalian phenotype. Here, we show that germ-line inherited rDNA CN is associated with post-pubertal growth rate in rats and BMI in adult humans. rDNA CN variation is not associated with rRNA transcription rates in adult tissues, suggesting the mechanistic link occurs earlier in development. This is supported by our observation that it is growth rate and body mass, rather than obesity that are associated with copy number and that these phenotypes emerge prior to adulthood. We present hypotheses for future investigation into the mechanistic basis of this association.

Ribosomal DNA copy number is associated with body mass in humans and other mammals