Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height

Genomewide linkage analysis has been extremely successful at identification of the genetic variation underlying single-gene disorders. However, linkag e analysis has been less successful for common human diseases and other com plex traits in which multiple genetic and environmental factors interact to influence disease risk. We hypothesized that a highly heritable complex tr ait, in which the contribution of environmental factors was relatively limi ted, might be more amenable to linkage analysis. We therefore chose to stud y stature (adult height), for which heritability is 75%-90% (Phillips and M atheny 1990; Carmichael and McGue 1995; Preece 1996; Silventoinen et al. 20 00). We reanalyzed genomewide scans from four populations for which genotyp e and height data were available, using a variance-components method implem ented in GENEHUNTER 2.0 (Pratt et al. 2000). The populations consisted of 4 08 individuals in 58 families from the Botnia region of Finland, 753 indivi duals in 183 families from other parts of Finland, 746 individuals in 179 f amilies from Southern Sweden, and 420 individuals in 63 families from the S aguenay-Lac-St.-Jean region of Quebec. Four regions showed evidence of link age to stature: 6q24-25, multipoint LOD score 3.85 at marker D6S1007 in Bot nia (genomewide P<.06), 7q31.3-36 (LOD 3.40 at marker D7S2195 in Sweden, P< .02), 12p11.2-q14 (LOD 3.35 at markers D12S10990-D12S398 in Finland,P<.05) and 13q32-33 (LOD 3.56 at markers D13S779-D13S797 in Finland, P<.05). In a companion article (Perola et al. 2001 [in this issue]), strong supporting e vidence is obtained for linkage to the region on chromosome 7. These studie s suggest that highly heritable complex traits such as stature may be genet ically tractable and provide insight into the genetic architecture of compl ex traits.