Genomic Imprinting as a Potential Source of Missing Heritability of Mouse Body Mass Index

Abstract Text: Epigenetics, especially genomic imprinting, has been suggested to cause genetic variation and contribute to narrow sense heritability of complex traits. We conducted a GWAS-like study using a mouse population with 1,940 individuals and 10,021 SNP markers. Body mass index was chosen as target trait, presumably affected by genomic imprinting, according to published studies on humans and mice. Results showed that ignoring imprinting in GWAS may produce up to a 60% loss of marker-explained variance. A 22% "underestimate" of narrow sense heritability was observed when both pedigree and marker information were considered together.  In conclusion, when imprinting exists, an additive model is not capable of capturing phenotypic variation attributed to this epigenetic mechanism, leading to underestimates of heritability in GWAS studies, and so contributing to the so-called missing heritability.

Keywords: genomic imprinting, missing heritability, mouse body mass index