Stature Quantitative Trait Locus 3

For a discussion of genetic heterogeneity of quantitative trait loci for stature (STQTL), see STQTL1 (606255).

Mapping

Hirschhorn et al. (2001) analyzed genomewide scans in 4 populations using a variance-components method, using stature as a quantitative trait locus, and found strong evidence for linkage to chromosome 12p11.2-q14 in a Finnish population (maximum lod = 3.35 at markers D12S10990-D12S398, p less than 0.05).

Xu et al. (2002) performed segregation and linkage analyses for adult height in a population of 200 Dutch families, each of which was ascertained through a proband with asthma. Modest support for linkage to 12q1 was observed; lod = 1.86 at D12S375.

Timpson et al. (2009) performed a genomewide association study of bone mineral density (see 601884) and related traits in 1,518 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). There was an association between bone mineral density and 4 SNPs (rs2016266, rs4759021, rs6580942, rs10876432) on chromosome 12p13 surrounding the SP7 (606633) and AAAS (605378) genes. Metaanalysis of 2 previous studies revealed strong association between the 4 SNPs in the 12p13 region and adult lumbar spine bone mineral density (p = 9.9 x 10(-11)). The authors genotyped a further 3,692 children from ALSPAC and confirmed the association in the combined ALSPAC set with whole body bone mineral density in children under age 9 (combined set p = 3.1 x 10(-5) for rs2016266). Moreover, all 4 SNPs were associated with height in ALSPAC children (p = 3.7 x 10(-5) for rs2016266), but not with weight or body mass index, and adjusting for height in the combined ALSPAC set attenuated the associations with bone mineral density. Timpson et al. (2009) concluded that genetic variants in the region of the SP7 gene are associated with bone mineral density in children and adults, probably through primary effects on growth.

Molecular Genetics

Lorentzon et al. (2000) investigated the vitamin D receptor (VDR; 601769) gene polymorphisms, BsmI and TaqI, in 90 healthy Caucasian males. Boys with the BB genotype were shorter at birth (p = 0.01) and grew less from birth to age 16.9 +/- 0.3 (p = 0.01) than their Bb and bb counterparts. Both during puberty (age 16.9 +/- 0.3) and after puberty (age 19.3 +/- 0.7), the BB boys were shorter (p = 0.005 - 0.008). The VDR allelic variants alone contributed to 8% of the total variation in adult height.

In a study of the VDR and adult height in 1,873 white subjects from 406 nuclear families, Xiong et al. (2005) found within-family associations with height at BsmI and TaqI loci (p = 0.048 and 0.039, respectively). Analyses based on BsmI/TaqI haplotypes showed linkage (p = 0.05) and association (p = 0.001) with height.