THBS2 and lumbar disc herniation: A further example of the combined effect of two unlinked SNPs is provided by an intronic SNP in the thrombospondin 2 (THBS2) gene (c.1478-8C>T; rs 9406328) and a missense SNP in the metalloproteinase 9 (MMP9) gene (Gln279Arg; rs17576), which together increase the risk of lumbar disc herniation (Hirose et al. 2008).