engleski

Common variants of the JAZF1 gene associated with height identified by linkage and whole genome association analysis

Identification of genes for human height has been of interest for decades, but only recently have a number candidate genes started to been identified. We have performed a linkage analysis and a genome wide association study for height in about 4, 000 individuals from five European populations. A total of 5 chromosomal regions showed suggestive linkage and in one of these regions (on chromosome 7), two SNPs (rs849140 and rs1635852) were associated with height (nominal p = 7.0 x 10-8 and p = 9.6 x 10-7 respectively). In total five SNPs across the genome showed an association with height that reached the threshold of genome wide significance (nominal p < 1.6 x 10-7). The association to height were replicated for two SNPs (rs849140 and rs1635852 ) using three independent studies (N = 32 225, N = 2 000 and N = 6 000) with p-values down to p = 7.7 ´ 10-5. Both these SNPs are located in the JAZF1 gene, a gene that has recently been associated with type II diabetes, prostate and endometrial cancer. JAZF1 is a transcriptional repressor of NR2C2, a gene which when knocked-out in mice results in low IGF1 serum concentrations, perinatal and early postnatal hypoglycaemia and growth retardation. Both the linkage and association analysis independently identified the JAZF1 region affecting human height. Since we have demonstrated, through replication in additional populations, the consistency of the association between the two JAZF1 SNPs and height and since this the gene has a key function in the metabolism of growth, JAZF1 represent one of the strongest candidates for human height so far identified.

SNP; height; GWA; linkage

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