Quantitative trait loci on chromosomes 2p, 4p, and 13q influence bone mineral density of the forearm and hip in Mexican Americans.
We performed a genome scan using BMD data of the forearm and hip on 664 individuals in 29 Mexican-American families. We obtained evidence for QTL on chromosome 4p, affecting forearm BMD overall, and on chromosomes 2p and 13q, affecting hip BMD in men.


BACKGROUND
The San Antonio Family Osteoporosis Study (SAFOS) was designed to identify genes and environmental factors that influence bone mineral density (BMD) using data from large Mexican-American families.


METHODS
We performed a genome-wide linkage analysis using 416 highly polymorphic microsatellite markers spaced approximately 9.5 cM apart to locate and identify quantitative trait loci (QTL) that affect BMD of the forearm and hip. Multipoint variance components linkage analyses were done using data on all 664 subjects, as well as two subgroups of 259 men and 261 premenopausal women, from 29 families for which genotypic and phenotypic data were available.


RESULTS
We obtained significant evidence for a QTL affecting forearm (radius midpoint) BMD in men and women combined on chromosome 4p near D4S2639 (maximum LOD = 4.33, genomic p = 0.006) and suggestive evidence for a QTL on chromosome 12q near locus D12S2070 (maximum conditional LOD = 2.35). We found suggestive evidence for a QTL influencing trochanter BMD on chromosome 6 (maximum LOD = 2.27), but no evidence for QTL affecting the femoral neck in men and women combined. In men, we obtained evidence for QTL affecting neck and trochanter BMD on chromosomes 2p near D2S1780 (maximum LOD = 3.98, genomic p = 0.013) and 13q near D13S788 (maximum LOD = 3.46, genomic p = 0.039), respectively. We found no evidence for QTL affecting forearm or hip BMD in premenopausal women.


CONCLUSIONS
These results provide strong evidence that a QTL on chromosome 4p affects radius BMD in Mexican-American men and women, as well as evidence that QTL on chromosomes 2p and 13q affect hip BMD in men. Our results are consistent with some reports in humans and mice. J Bone Miner Res 2003;18:2245-2252
Kammerer
Candace M
CM
Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 15261, USA. ckammerer@hgen.pitt.edu
Schneider
Jennifer L
JL
Cole
Shelley A
SA
Hixson
James E
JE
Samollow
Paul B
PB
O'Connell
Jeffrey R
JR
Perez
Reina
R
Dyer
Thomas D
TD
Almasy
Laura
L
Blangero
John
J
Bauer
Richard L
RL
Mitchell
Braxton D
BD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics / Q000502:physiology*; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005260:Female; D005542:Forearm; D006621:Hip Joint; D006801:Humans; D008126:Lod Score; D017058:Mexican Americans / Q000235:genetics*; D008875:Middle Aged; D040641:Quantitative Trait Loci; D013781:Texas