Confirmation linkage study in support of the X chromosome harbouring a QTL underlying human height variation

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Abstract
Human height is a complex trait determined by both genetic and environmental factors. An initial whole genome study showed several genomic regions with suggestive linkage to height in a sample of 630 subjects from 53 human pedigrees. The present study was conducted in an extended sample of 1816 subjects from 79 pedigrees in an attempt to replicate and confirm the results of the previous whole genome scan. Xq24–25 on the X chromosome was confirmed as the region suggestive of linkage to height. In the previous whole genome study, a microsatellite marker of the region DXS1001 achieved a two point LOD score of 1.91 for linkage to height. In the present study on the 79 pedigrees, another marker of the same region, DXS8067, which is only 2.7 cM away from the former marker, attained a higher two point LOD score of 2.66. Moreover, the region’s significant linkage to height was sustained, with a two point LOD score of 1.00 achieved in a subset of the current sample (1026 subjects from 26 new pedigrees), which is independent of the original 630 subjects used in the whole genome study. Our results—together with identification of several syndromes with short stature, which are in linkage to Xq24–25—strongly suggest that this region may harbour a quantitative trait locus (QTL) underlying human height variation. Human height is a typical complex trait determined by both genetic and environmental factors. Nutritional status and diseases are the most important environmental factors controlling human linear growth.1–4 However, genetic factors play a more dominant role in height determination. This is indicated by a significant familial aggregation of the trait, translating into a heritability of well above 50%.5–9 The search for genes underlying height variation has long been an endeavour in the field of genetic studies of complex traits. …