Cytogenetic location: 7q21 Genomic coordinates (GRCh38): 7:77,900,001-98,400,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 7q21 | {Stature QTL 11} | 612223 | 2 |
For a discussion of genetic heterogeneity of quantitative trait loci for stature (STQTL), see STQTL1 (606255).
To identify genetic variants influencing adult human height, Weedon et al. (2008) used genomewide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. They identified strong association with a single-nucleotide polymorphism (SNP) in the CDK6 gene (603368), rs2282978 (combined P = 7.8 x 10(-23)). The CDK6 gene is located on chromosome 7q21 and encodes a cyclin-dependent kinase implicated in cell cycle progression. Overall, Weedon et al. (2008) identified 20 variants associated with adult height (P less than 5 x 10(-7), with 10 reaching P less than 1 x 10(-10)). The 20 SNPs together explain approximately 3% of height variation, with an approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. Each of the robustly associated variants identified in the study altered height by between approximately 0.2 and 0.6 centimeters per allele.
Lettre et al. (2008) carried out a metaanalysis of genomewide association study data of height for 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in greater than 10,000 subjects. A SNP in the CDK6 gene, rs2040494 showed strong association (P = 3.8 x 10(-7)). Lettre et al. (2008) identified 12 loci in all that were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)) and that together accounted for approximately 2% of the population variation in height. Individuals with 8 or fewer height-increasing alleles and 16 or more height-increasing alleles differed in height by approximately 3.5 cm. The combined effect size of the rs2040494 C allele was -0.262 cm.
Gudbjartsson et al. (2008) searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans, and 1,148 African Americans. The authors then combined their data with previously published results from the Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes for BioMedical Research (2007) on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. Two SNPs in the CDK6 gene, rs2282978 and rs11765954, achieved P values of 9.8 x 10(-9) and 6.9 x 10(-8), respectively. In all Gudbjartsson et al. (2008) identified 27 regions of the genome with 1 or more sequence variants showing significant association with height.
To identify loci associated with stature, Soranzo et al. (2009) performed a genomewide scan in 12,611 participants followed by replication in an additional 7,187 individuals. All participants were of British or Dutch descent. Soranzo et al. (2009) confirmed the association with rs2282978 (combined P = 1.2 x 10(-8)).
Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes for BioMedical Research. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316: 1331-1336, 2007. [PubMed: 17463246] [Full Text: https://doi.org/10.1126/science.1142358]
Gudbjartsson, D. F., Walters, G. B., Thorleifsson, G., Stefansson, H., Halldorsson, B. V., Zusmanovich, P., Sulem, P., Thorlacius, S., Gylfason, A., Steinberg, S., Helgadottir, A., Ingason, A., and 25 others. Many sequence variants affecting diversity of adult human height. Nature Genet. 40: 609-615, 2008. [PubMed: 18391951] [Full Text: https://doi.org/10.1038/ng.122]
Lettre, G., Jackson, A. U., Gieger, C., Schumacher, F. R., Berndt, S. I., Sanna, S., Eyheramendy, S., Voight, B. F., Butler, J. L., Guiducci, C., Illig, T., Hackett, R., and 25 others. Identification of ten loci associated with height highlights new biological pathways in human growth. Nature Genet. 40: 584-591, 2008. [PubMed: 18391950] [Full Text: https://doi.org/10.1038/ng.125]
Soranzo, N., Rivadeneira, F., Chinappen-Horsley, U., Malkina, I., Richards, J. B., Hammond, N., Stolk, L., Nica, A., Inouye, M., Hofman, A., Stephens, J., Wheeler, E., and 26 others. Meta-analysis of genome-wide scans for human adult stature identifies novel loci and associations with measures of skeletal frame size. PLoS Genet. 5: e1000445, 2009. Note: Electronic Article. [PubMed: 19343178] [Full Text: https://doi.org/10.1371/journal.pgen.1000445]
Weedon, M. N., Lango, H., Lindgren, C. M., Wallace, C., Evans, D. M., Mangino, M., Freathy, R. M., Perry, J. R. B., Stevens, S., Hall, A. S., Samani, N. J., Shields, B., and 20 others. Genome-wide association analysis identifies 20 loci that influence adult height. Nature Genet. 40: 575-583, 2008. [PubMed: 18391952] [Full Text: https://doi.org/10.1038/ng.121]