TY - JOUR
T1 - Strong association between polymorphisms in ANKH locus and skeletal size traits
AU - Malkin, Ida
AU - Ermakov, Sergey
AU - Kobyliansky, Eugene
AU - Livshits, Gregory
N1 - Funding Information:
Acknowledgements This study was performed in partial fulfillment of the doctoral degree requirements of Sergey Ermakov. We wish to thank Dr. Svetlana Trofimov (Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University) for help in DNA preparation, Dr. Mira Korner and her staff (The Center for Genomic Technologies, The Institute of Life Sciences, The Hebrew University of Jerusalem) for the genotyping of the samples, and Galit Schwartz (Applied Biosystems, Agentek-Israel) for her assistance. This study was supported by the Israel National Science Foundation (Grant No. 1042/04).
PY - 2006/8
Y1 - 2006/8
N2 - Loss of bone strength is the main determinant of bone fragility. Bone strength is directly dependent on bone size (BS). A substantial portion of BS variation is attributable to genetic effects. However, the list of genes and allelic variants involved in the determination of BS variation is far from being complete. Polymorphisms in the ANKH gene have been shown to be associated with radiographic hand BS-related phenotypes. The present study examined the possible association of the ANKH gene with skeletal size and shape in order to test the universality of the ANKH effect on BS traits. Our sample consisted of a total of 212 ethnically homogeneous nuclear families (743 individuals) of European origin. Each individual was measured for body height, weight, and several other anthropometrical measurements, and genotyped for nine polymorphic markers (the average heterozygosity level was 0.4). We observed significant associations with practically all the anthropometrical phenotypes studied. More specifically, we found associations with body weight and height, limb length (P ≤ 0.001; promoter region). After adjustment for body height, we demonstrated the substantial association increase for biacromial breadth (P=0.0012; some 140 kb downstream from ANKH) and vertebral column length (P = 0.0008; exons 2-7 region). The majority of the observed associations persisted even after correction for multiple testing. For the first time the reliable evidence in support of universality of ANKH gene polymorphisms effect on bone size was provided.
AB - Loss of bone strength is the main determinant of bone fragility. Bone strength is directly dependent on bone size (BS). A substantial portion of BS variation is attributable to genetic effects. However, the list of genes and allelic variants involved in the determination of BS variation is far from being complete. Polymorphisms in the ANKH gene have been shown to be associated with radiographic hand BS-related phenotypes. The present study examined the possible association of the ANKH gene with skeletal size and shape in order to test the universality of the ANKH effect on BS traits. Our sample consisted of a total of 212 ethnically homogeneous nuclear families (743 individuals) of European origin. Each individual was measured for body height, weight, and several other anthropometrical measurements, and genotyped for nine polymorphic markers (the average heterozygosity level was 0.4). We observed significant associations with practically all the anthropometrical phenotypes studied. More specifically, we found associations with body weight and height, limb length (P ≤ 0.001; promoter region). After adjustment for body height, we demonstrated the substantial association increase for biacromial breadth (P=0.0012; some 140 kb downstream from ANKH) and vertebral column length (P = 0.0008; exons 2-7 region). The majority of the observed associations persisted even after correction for multiple testing. For the first time the reliable evidence in support of universality of ANKH gene polymorphisms effect on bone size was provided.
UR - http://www.scopus.com/inward/record.url?scp=33745728421&partnerID=8YFLogxK
U2 - 10.1007/s00439-006-0173-6
DO - 10.1007/s00439-006-0173-6
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AN - SCOPUS:33745728421
SN - 0340-6717
VL - 120
SP - 42
EP - 51
JO - Human Genetics
JF - Human Genetics
IS - 1
ER -