Human Molecular Genetics, 2001, Vol. 10, No. 21 2447-2452
© 2001 Oxford University Press
Variance component linkage analysis indicates a QTL for femoral neck bone mineral density on chromosome 1p36
1Department of Research, AI duPont Hospital for Children, Wilmington, DE 19899, USA 2Department of Oncology, Biology and Genetics, University of Genoa, Genoa, Italy, 3Department of Health Science, University of Genoa, Genoa, Italy, 4McGill Bone Centre, Montreal, Canada and 5Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA, USA
Osteoporosis is a common condition characterized by reduced skeletal strength and increased susceptibility to fracture. Eight million Americans over the age of 50 have osteoporosis of the femoral neck. The most important risk factor for osteoporosis is low bone mineral density (BMD), and several epidemiological studies have shown the importance of genetic factors in determining variability of BMD. An initial genome screen in seven large pedigrees suggested that a candidate region conferring susceptibility to low BMD of the femoral neck was located on chromosome 1p36. We have now confirmed and extended this finding by analyzing nine microsatellite markers spanning a 40 cM interval across the candidate region in an expanded sample of 42 families. Heritability of femoral neck BMD was estimated as 0.51 ± 0.13 in these families, after accounting for the effects of age, sex, body mass index, height and weight. Variance component linkage analysis yielded a maximum multipoint LOD score of 3.53 for linkage of femoral neck BMD to a quantitative trait locus (QTL) located near marker D1S214. The associated empirical P-value by simulation analysis was equal to 0.0001. The results strongly support the hypothesis that a major QTL controlling femoral neck BMD is located on chromosome 1p36.2–p36.3, and further analysis of candidate genes in this region is warranted.
+ To whom correspondence should be addressed at: Department of Research, AI duPont Hospital for Children, AR 210A, PO Box 269, Wilmington, DE 19899, USA. Tel: +1 302 651 6838; Fax: +1 302 651 6895; Email: mdevoto@nemours.org
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