Runs of homozygosity identify a recessive locus 12q21.31 for human adult height

Background: Runs of homozygosity (ROHs) have recently been proposed to have potential recessive significance for complex traits. Human adult height is a classic complex trait with heritability estimated up to 90%, and recessive loci that contribute to adult height variation have been identified. Methods: Using the Affymetrix 500K array set, we performed a genome-wide ROHs analysis to identify genetic loci for adult height in a discovery sample including 998 unrelated Caucasian subjects from the midwest United States. For the significant ROHs identified, we replicated these findings in a family-based sample of 8385 Caucasian subjects from the Framingham Heart Study (FHS). Results: Our results revealed one ROH, located in 12q21.31, that had a strong association with adult height variation both in the discovery (P = 6.69 × 10^-6) and replication samples (P = 5.40 × 10^-5). We further validated the presence of this ROH using the HapMap sample. Conclusion: Our findings open a new avenue for identifying loci with recessive contributions to adult height variation. Further molecular and functional studies are needed to explore and clarify the potential mechanism.