Genome screen for quantitative trait loci underlying normal variation in femoral structure

Daniel L. Koller, Guangda Liu, Michael Econs, Siu Hui, Phillip A. Morin, Geoff Joslyn, Lawrence A. Rodriguez, P. Michael Conneally, Joe C. Christian, C. Conrad Johnston, Tatiana Foroud, Munro Peacock

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Femoral structure contributes to bone strength at the proximal femur and predicts hip fracture risk independently of bone mass. Quantitative components of femoral structure are highly heritable traits. To identify genetic loci underlying variation in these structural phenotypes, we conducted an autosomal genome screen in 309 white sister pairs. Seven structural variables were measured from femoral radiographs and used in multipoint sib-pair linkage analyses. Three chromosomal regions were identified with significant evidence of linkage (log10 of the odds ratio [LOD] > 3.6) to at least one femoral structure phenotype. The maximum LOD score of 4.3 was obtained for femur neck axis length on chromosome 5q. Evidence of linkage to chromosome 4q was found with both femur neck axis length (LOD = 3.9) and midfemur width (LOD = 3.5). Significant evidence of linkage also was found to chromosome 17q, with a LOD score of 3.6 for femur head width. Two additional chromosomal regions 3q and 19p gave suggestive (LOD > 2.2) evidence of linkage with at least two of the structure phenotypes. Chromosome 3 showed evidence of linkage with pelvic axis length (LOD = 3.1), midfemur width (LOD = 2.8), and femur head width (LOD = 2.3), spanning a broad (60 cm) region of chromosome 3q. Linkage to chromosome 19 was supported by two phenotypes, femur neck axis length (LOD = 2.8) and femur head width (LOD = 2.8). This study is the first genome screen for loci underlying variation in femoral structure and represents an important step toward identifying genes contributing to the risk of osteoporotic hip fracture in the general population.

Original languageEnglish
Pages (from-to)985-991
Number of pages7
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume16
Issue number6
StatePublished - 2001

Fingerprint

Quantitative Trait Loci
Thigh
Odds Ratio
Genome
Femur Head
Femur Neck
Chromosomes
Phenotype
Hip Fractures
Chromosomes, Human, Pair 19
Bone and Bones
Osteoporotic Fractures
Chromosomes, Human, Pair 3
Genetic Loci
Femur

Keywords

  • Femoral structure
  • Genetics
  • Hip fracture
  • Osteoporosis
  • Quantitative trait locus

ASJC Scopus subject areas

  • Surgery

Cite this

Genome screen for quantitative trait loci underlying normal variation in femoral structure. / Koller, Daniel L.; Liu, Guangda; Econs, Michael; Hui, Siu; Morin, Phillip A.; Joslyn, Geoff; Rodriguez, Lawrence A.; Michael Conneally, P.; Christian, Joe C.; Conrad Johnston, C.; Foroud, Tatiana; Peacock, Munro.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 16, No. 6, 2001, p. 985-991.

Research output: Contribution to journalArticle

Koller, Daniel L. ; Liu, Guangda ; Econs, Michael ; Hui, Siu ; Morin, Phillip A. ; Joslyn, Geoff ; Rodriguez, Lawrence A. ; Michael Conneally, P. ; Christian, Joe C. ; Conrad Johnston, C. ; Foroud, Tatiana ; Peacock, Munro. / Genome screen for quantitative trait loci underlying normal variation in femoral structure. In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2001 ; Vol. 16, No. 6. pp. 985-991.
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AU - Koller, Daniel L.

AU - Liu, Guangda

AU - Econs, Michael

AU - Hui, Siu

AU - Morin, Phillip A.

AU - Joslyn, Geoff

AU - Rodriguez, Lawrence A.

AU - Michael Conneally, P.

AU - Christian, Joe C.

AU - Conrad Johnston, C.

AU - Foroud, Tatiana

AU - Peacock, Munro

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N2 - Femoral structure contributes to bone strength at the proximal femur and predicts hip fracture risk independently of bone mass. Quantitative components of femoral structure are highly heritable traits. To identify genetic loci underlying variation in these structural phenotypes, we conducted an autosomal genome screen in 309 white sister pairs. Seven structural variables were measured from femoral radiographs and used in multipoint sib-pair linkage analyses. Three chromosomal regions were identified with significant evidence of linkage (log10 of the odds ratio [LOD] > 3.6) to at least one femoral structure phenotype. The maximum LOD score of 4.3 was obtained for femur neck axis length on chromosome 5q. Evidence of linkage to chromosome 4q was found with both femur neck axis length (LOD = 3.9) and midfemur width (LOD = 3.5). Significant evidence of linkage also was found to chromosome 17q, with a LOD score of 3.6 for femur head width. Two additional chromosomal regions 3q and 19p gave suggestive (LOD > 2.2) evidence of linkage with at least two of the structure phenotypes. Chromosome 3 showed evidence of linkage with pelvic axis length (LOD = 3.1), midfemur width (LOD = 2.8), and femur head width (LOD = 2.3), spanning a broad (60 cm) region of chromosome 3q. Linkage to chromosome 19 was supported by two phenotypes, femur neck axis length (LOD = 2.8) and femur head width (LOD = 2.8). This study is the first genome screen for loci underlying variation in femoral structure and represents an important step toward identifying genes contributing to the risk of osteoporotic hip fracture in the general population.

AB - Femoral structure contributes to bone strength at the proximal femur and predicts hip fracture risk independently of bone mass. Quantitative components of femoral structure are highly heritable traits. To identify genetic loci underlying variation in these structural phenotypes, we conducted an autosomal genome screen in 309 white sister pairs. Seven structural variables were measured from femoral radiographs and used in multipoint sib-pair linkage analyses. Three chromosomal regions were identified with significant evidence of linkage (log10 of the odds ratio [LOD] > 3.6) to at least one femoral structure phenotype. The maximum LOD score of 4.3 was obtained for femur neck axis length on chromosome 5q. Evidence of linkage to chromosome 4q was found with both femur neck axis length (LOD = 3.9) and midfemur width (LOD = 3.5). Significant evidence of linkage also was found to chromosome 17q, with a LOD score of 3.6 for femur head width. Two additional chromosomal regions 3q and 19p gave suggestive (LOD > 2.2) evidence of linkage with at least two of the structure phenotypes. Chromosome 3 showed evidence of linkage with pelvic axis length (LOD = 3.1), midfemur width (LOD = 2.8), and femur head width (LOD = 2.3), spanning a broad (60 cm) region of chromosome 3q. Linkage to chromosome 19 was supported by two phenotypes, femur neck axis length (LOD = 2.8) and femur head width (LOD = 2.8). This study is the first genome screen for loci underlying variation in femoral structure and represents an important step toward identifying genes contributing to the risk of osteoporotic hip fracture in the general population.

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