Variations in RANK gene are associated with adult height in Caucasians

Height is a complex trait significantly influenced by genetic factors, with heritability ranging from 48% to 98%. Previous studies have yielded a number of important genomic regions that may account for the variation of height in human populations. However, more 'height' genes still wait for identification. Recent studies have revealed that tumor necrosis factor receptor superfamily member 11a (RANK) is a vital factor for chondroclastic/osteoclastic differentiation and activity that influence the morphology of growth plates and linear bone growth. Despite its importance, little effort has been made to find out whether the RANK polymorphisms are associated with adult height variation in normal populations. Herein, we performed a family based association test (FBAT) in 1873 white subjects from 405 nuclear families. Among eighteen single nucleotide polymorphisms (SNPs) and seven blocks, SNP rs6567274 was detected to be significant even after multiple-testing correction. In corroboration with single-locus analysis, a major haplotype in block 5 bearing the variant "T" of rs6567274 was significantly associated with higher stature. Our findings firstly suggested the RANK polymorphisms might contribute to adult height variation. Further researches need to be launched to replicate the present results and further unravel the molecular mechanism underlying the significant associations discovered.