TY - JOUR
T1 - Bivariate genome-wide linkage analysis of femoral bone traits and leg lean mass
T2 - Framingham study
AU - Karasik, David
AU - Zhou, Yanhua
AU - Adrienne Cupples, L.
AU - Hannan, Marian T.
AU - Kiel, Douglas P.
AU - Demissie, Serkalem
PY - 2009/4
Y1 - 2009/4
N2 - The risk of osteoporotic fracture is a function of both applied muscle mass and bone tissue distribution. Leg lean mass (LLM) and femoral bone geometry are both known to have substantial genetic components. Therefore, we estimated shared heritability (h2) and performed linkage analysis to identify chromosomal regions governing both LLM and bone geometry. A genome-wide scan (using 636 microsatellite markers) for linkage analyses was performed on 1346 adults from 327 extended families of the Framingham study. DXA measures were LLM, femoral neck length, neck-shaft angle (NSA), subperiosteal width, cross-sectional area (CSA), and section modulus (Z) at the femoral narrow neck and shaft (S) regions. Variance component linkage analysis was performed on normalized residuals (adjusted for age, height, BMI, and estrogen status in women). The results indicated substantial h2 for LLM (0.42 ± 0.07) that was comparable to bone geometry traits. Phenotypic correlations between LLM and bone geometry phenotypes ranged from 0.033 with NSA (p > 0.05) to 0.251 with S-Z (p < 0.001); genetic correlations ranged from 0.087 (NSA, ρ > 0.05) to 0.454 (S-Z, ρ < 0.001). Univariate linkage analysis of covariate-adjusted LLM identified no chromosomal regions with LOD scores ≥2.0; however, bivariate analysis identified two loci with LOD scores >3.0, shared by LLM with S-CSA on chromosome 12pl2.3-12pl3.2, and with NSA, on 14q21.3-22.1. In conclusion, we identified chromosomal regions potentially linked to both LLM and femoral bone geometry. Identification and subsequent characterization of these shared loci may further elucidate the genetic contributions to both osteoporosis and sarcopenia.
AB - The risk of osteoporotic fracture is a function of both applied muscle mass and bone tissue distribution. Leg lean mass (LLM) and femoral bone geometry are both known to have substantial genetic components. Therefore, we estimated shared heritability (h2) and performed linkage analysis to identify chromosomal regions governing both LLM and bone geometry. A genome-wide scan (using 636 microsatellite markers) for linkage analyses was performed on 1346 adults from 327 extended families of the Framingham study. DXA measures were LLM, femoral neck length, neck-shaft angle (NSA), subperiosteal width, cross-sectional area (CSA), and section modulus (Z) at the femoral narrow neck and shaft (S) regions. Variance component linkage analysis was performed on normalized residuals (adjusted for age, height, BMI, and estrogen status in women). The results indicated substantial h2 for LLM (0.42 ± 0.07) that was comparable to bone geometry traits. Phenotypic correlations between LLM and bone geometry phenotypes ranged from 0.033 with NSA (p > 0.05) to 0.251 with S-Z (p < 0.001); genetic correlations ranged from 0.087 (NSA, ρ > 0.05) to 0.454 (S-Z, ρ < 0.001). Univariate linkage analysis of covariate-adjusted LLM identified no chromosomal regions with LOD scores ≥2.0; however, bivariate analysis identified two loci with LOD scores >3.0, shared by LLM with S-CSA on chromosome 12pl2.3-12pl3.2, and with NSA, on 14q21.3-22.1. In conclusion, we identified chromosomal regions potentially linked to both LLM and femoral bone geometry. Identification and subsequent characterization of these shared loci may further elucidate the genetic contributions to both osteoporosis and sarcopenia.
KW - Body composition
KW - Bone geometry
KW - Osteoporosis
KW - Proximal femur
KW - Quantitative trait loci
KW - Sarcopenia
UR - http://www.scopus.com/inward/record.url?scp=65549137512&partnerID=8YFLogxK
U2 - 10.1359/jbmr.081222
DO - 10.1359/jbmr.081222
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C2 - 19063671
AN - SCOPUS:65549137512
SN - 0884-0431
VL - 24
SP - 710
EP - 718
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 4
ER -