Common variants in the GDF5-UQCC region are associated with variation in human height

Abstract

Identifying genetic variants that influence human height will advance our understanding of skeletal growth and development. Several rare genetic variants have been convincingly and reproducibly associated with height in mendelian syndromes, and common variants in the transcription factor gene HMGA2 are associated with variation in height in the general population. Here we report genome-wide association analyses, using genotyped and imputed markers, of 6,669 individuals from Finland and Sardinia, and follow-up analyses in an additional 28,801 individuals. We show that common variants in the osteoarthritis-associated locus GDF5-UQCC contribute to variation in height with an estimated additive effect of 0.44 cm (overall P < 10(-15)). Our results indicate that there may be a link between the genetic basis of height and osteoarthritis, potentially mediated through alterations in bone growth and development.

Figure 1. Evidence of (A) association with height and (B) linkage disequilibrium around GDF5 and BFZB/C20orf44/UQCC

All genotyped or imputed SNPs in the SardiNIA and FUSION GWA studies are plotted with association p-values (additive test) compared to genomic position in NCBI Build 35 (gray circles, red circles for labeled SNPs). Yellow squares indicate p-values for SNPs analyzed in a portion of follow up samples (FUSION Stage 1 and 2, SardiNIA, DGI, and ARIC studies). The green triangle indicates rs6060369 analyzed in all GWAS and follow up samples. Patterns of linkage disequilibrium (r²) for two of the HapMap populations (CEU, Utah residents with European ancestry, and YRI, Yoruba)³⁰ are plotted and colored with a 15 color red-green-blue scale, to represent values ranging from high (red), to intermediate (green), to low (blue).