Mapping quantitative trait loci for cross-sectional geometry at the femoral neck.
A genome-wide linkage scan was performed in a sample of 79 multiplex pedigrees to identify genomic regions linked to femoral neck cross-sectional geometry. Potential quantitative trait loci were detected at several genomic regions, such as 10q26, 20p12-q12, and chromosome X.


BACKGROUND
Bone geometry is an important determinant of bone strength and osteoporotic fractures. Previous studies have shown that femoral neck cross-sectional geometric variables are under genetic controls. To identify genetic loci underlying variation in femoral neck cross-sectional geometry, we conducted a whole genome linkage scan for four femoral neck cross-sectional geometric variables in 79 multiplex white pedigrees.


METHODS
A total of 1816 subjects from 79 pedigrees were genotyped with 451 microsatellite markers across the human genome. We performed linkage analyses on the entire data, as well as on men and women separately.


RESULTS
Significant linkage evidence was identified at 10q26 for buckling ratio (LOD = 3.27) and Xp11 (LOD = 3.45) for cortical thickness. Chromosome region 20p12-q12 showed suggestive linkage with cross-sectional area (LOD = 2.33), cortical thickness (LOD = 2.09), and buckling ratio (LOD = 1.94). Sex-specific linkage analyses further supported the importance of 20p12-q12 for cortical thickness (LOD = 2.74 in females and LOD = 1.88 in males) and buckling ratio (LOD = 5.00 in females and LOD = 3.18 in males).


CONCLUSIONS
This study is the first genome-wide linkage scan searching for quantitative trait loci underlying femoral neck cross-sectional geometry in humans. The identification of the genes responsible for bone geometric variation will improve our knowledge of bone strength and aid in development of diagnostic approaches and interventions for osteoporotic fractures.
Shen
Hui
H
Osteoporosis Research Center, Creighton University, Omaha, Nebraska 68131, USA.
Long
Ji-Rong
JR
Xiong
Dong-Hai
DH
Liu
Yong-Jun
YJ
Liu
Yao-Zhong
YZ
Xiao
Peng
P
Zhao
Lan-Juan
LJ
Dvornyk
Volodymyr
V
Zhang
Yuan-Yuan
YY
Rocha-Sanchez
Sonia
S
Liu
Peng-Yuan
PY
Li
Jin-Long
JL
Deng
Hong-Wen
HW
D015502:Absorptiometry, Photon; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D005272:Femur Neck / Q000033:anatomy & histology*; D008040:Genetic Linkage / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D025341:Principal Component Analysis; D040641:Quantitative Trait Loci / Q000235:genetics*; D012737:Sex Factors; D044465:White People / Q000235:genetics