Molecular genetic studies of gene identification for osteoporosis: a 2004 update

Abstract

This review summarizes comprehensively the most important and representative molecular genetics studies of gene identification for osteoporosis published up to the end of December 2004. It is intended to constitute a sequential update of our previously published review covering the available data up to the end of 2002. Evidence from candidate gene association studies and genome-wide linkage studies in humans, as well as quantitative trait locus mapping animal models are reviewed separately. Studies of transgenic and knockout mice models relevant to osteoporosis are summarized. An important extension of this update is incorporation of functional genomic studies (including DNA microarrays and proteomics) on osteogenesis and osteoporosis, in light of the rapid advances and the promising prospects of the field. Comments are made on the most notable findings and representative studies for their potential influence and implications on our present understanding of genetics of osteoporosis. The format adopted by this review should be ideal for accommodating future new advances and studies.

FIG. 1

Statistical power for quantitative traits using unrelated population sample, and the sample size distribution of osteoporosis-related association studies published during 2002–2004 (Table 1). In power estimation, QTLs were assumed to be responsible for 2% (♦ or ⋄), 1% (▪ or □), or 0.5% (▴ or ▵) of phenotypic variation, respectively. The power was estimated under an ideal situation, for which the tested marker was the QTL itself with the causal allele frequency of 0.3 and the QTL follows additive inheritance. The significance level was set as α = 0.01 (solid lines) or 0.001 (dashed lines). We set two different α levels because it was suggested that two studies with p < 0.01 or a single study with p < 0.001 is predictive of future replication.⁽³⁶⁾