Genome screen for QTLs contributing to normal variation in bone mineral density and osteoporosis

A major determinant of the risk for osteoporosis is peak bone mineral densi ty (BMD), which is largely determined by genetic factors. mie recently repo rted linkage of peak BMD in a large sample of healthy sister pairs to chrom osome 11q12-13. To identify additional loci underlying normal variations in peak BMD, we conducted an autosomal genome screen in 429 Caucasian sister pairs. Multipoint LOD scores were computed for BMD at four skeletal sites. Chromosomal regions with LOD scores above 1.85 were further pursued in an e xpanded sample of 595 sister pairs (464 Caucasians and 131 African-American s). The highest LOD score attained in the expanded sample was 3.86 at chromosom e 1q21-23 with lumbar spine BMD. Chromosome 5q33-35 gave a LOD score of 2.2 3 with femoral neck BMD. At chromosome 6p11-12, the 464 Caucasian pairs ach ieved a LOD score of 2.13 with lumbar spine BMD. Markers within the 11q12-1 3 region continued to support linkage to femoral neck BMD, although the pea k LOD score was decreased to 2.16 in the sample of 595 sibling pairs. Our s tudy is the largest genome screen to date for genes underlying variations i n peak BMD and represents an important step toward identifying genes contri buting to osteoporosis in the general population.