title: Genetics of disc-related disorders: current findings and lessons from other complex diseases.
abstract: Disc-related disorders are highly genetic conditions with heritability estimates of up to 75 % and yet, few genomic locations have been moderately associated with the disorders. Candidate gene studies have shown possible disease associations on loci and genes of 1p21.1 (COL11A1), 6q27 (THBS2), 9q22.31 (ASPN), 10p12.31 (SKT), 20q11.2 (GDF5) and 20q13.12 (MMP9). More recently, in 2012, the first genome-wide association study revealed variants on loci and genes of 3p26.2, 6p21.32 (HLA region) and 6q26 (PARK2) that associate with disc-related disorders. In many other complex diseases, large meta-analyses of hundreds of thousands of study subjects and loci have revealed remarkable pathways. As methodology is evolving rapidly, we have already stepped into the era of routinely sequencing all bases in all human exons and we are approaching the era of sequencing the entire genome of study subjects with common diseases. The past decade has taught us that the common variants seen throughout populations seem to have low effects in many common diseases, explain relatively little of the overall heritability of the diseases and demand thousands of study subjects to identify associations. It seems that familial rare variants play an important role in many common diseases leading us back to valuing studies with large families and isolated populations. Moreover, careful characterization of environmental conditions are needed to explore and determine gene-environment interactions as genes that increase disease risk in one context may not do so under another context.
authors.affiliation: Institute for Molecular Medicine Finland FIMM, University of Helsinki, P.O. Box 20, 00014, Helsinki, Finland.
authors.forename: Annu
authors.initials: A
authors.lastname: Näkki
authors.forename: Michele C
authors.initials: MC
authors.lastname: Battié
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
mesh_terms: D024161:Collagen Type XI / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D055428:Growth Differentiation Factor 5 / Q000235:genetics; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D011506:Proteins / Q000235:genetics; D019699:Thrombospondins / Q000235:genetics; D000099262:Thrombospondin 2
chemical_list: D024161:Collagen Type XI; D016326:Extracellular Matrix Proteins; D055428:Growth Differentiation Factor 5; D020780:Matrix Metalloproteinase 9; D011506:Proteins; D019699:Thrombospondins; D000099262:Thrombospondin 2; C439889:ASPN protein, human; C574182:COL11A1 protein, human; C525893:GDF5 protein, human; C569595:KIAA1217 protein, human; C579270:MMP9 protein, human