Evidence for a major gene for bone mineral-density/content in humandeng pedigrees identified via probands with extreme bone mineral density

H. W. Deng, G. Livshits, K. Yakovenko, F. H. Xu, T. Conway, K. M. Davies, H. Deng, Robert R. Recker

Research output: Contribution to journalReview article

48 Citations (Scopus)

Abstract

Bone mineral content (BMC) and/or bone mineral density (BMD, i.e. BMC scaled by bone size) are major determinants for osteoporosis, which is a serious health problem. The major determinant of variation in BMD/BMC is genetic. The few studies now available are inconsistent in the identification and/or even in the existence of major gene(s) for BMD/BMC. In 51 human pedigrees with 941 individuals (526 measured for phenotypes) identified via probands with extreme BMD values, we performed complex segregation analyses to test the existence of a genetic locus with a major effect on BMD/BMC variation. We analyzed BMD and BMC at the spine, hip and wrist jointly by employing, as the study phenotype, factor scores (FS) of the principle component that explains Ο 75% of the total BMD/BMC variation at the three sites. The results indicate that a major gene exists with a codominant effect that is responsible for Ο 16% of the FS variation when adjusted for significant effects of sex, body weight and age. A significant genotype- x -sex- x -age interaction was found, which may explain Ο 14% of the FS variation after adjusting for body weight. Testing of various models did not provide support for shared familial environmental effects but suggested the existence of residual polygenic effects, which may explain Ο 50% of the FS variation when adjusting for sex, body weight and age. This study indicates a promising aspect of studies to identify a major gene for BMD/BMC variation in our pedigrees identified via extreme probands.

Original languageEnglish
Pages (from-to)61-74
Number of pages14
JournalAnnals of Human Genetics
Volume66
Issue number1
DOIs
StatePublished - Jan 2002

Fingerprint

Pedigree
Bone Density
Genes
Body Weight
Phenotype
Genetic Loci
Wrist
Osteoporosis
Hip
Spine
Genotype
Bone and Bones
Health

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Genetics

Cite this

Evidence for a major gene for bone mineral-density/content in humandeng pedigrees identified via probands with extreme bone mineral density. / Deng, H. W.; Livshits, G.; Yakovenko, K.; Xu, F. H.; Conway, T.; Davies, K. M.; Deng, H.; Recker, Robert R.

In: Annals of Human Genetics, Vol. 66, No. 1, 01.2002, p. 61-74.

Research output: Contribution to journalReview article

Deng, H. W. ; Livshits, G. ; Yakovenko, K. ; Xu, F. H. ; Conway, T. ; Davies, K. M. ; Deng, H. ; Recker, Robert R. / Evidence for a major gene for bone mineral-density/content in humandeng pedigrees identified via probands with extreme bone mineral density. In: Annals of Human Genetics. 2002 ; Vol. 66, No. 1. pp. 61-74.
@article{b4afb53d09b946229e2c73408ee6533e,
title = "Evidence for a major gene for bone mineral-density/content in humandeng pedigrees identified via probands with extreme bone mineral density",
abstract = "Bone mineral content (BMC) and/or bone mineral density (BMD, i.e. BMC scaled by bone size) are major determinants for osteoporosis, which is a serious health problem. The major determinant of variation in BMD/BMC is genetic. The few studies now available are inconsistent in the identification and/or even in the existence of major gene(s) for BMD/BMC. In 51 human pedigrees with 941 individuals (526 measured for phenotypes) identified via probands with extreme BMD values, we performed complex segregation analyses to test the existence of a genetic locus with a major effect on BMD/BMC variation. We analyzed BMD and BMC at the spine, hip and wrist jointly by employing, as the study phenotype, factor scores (FS) of the principle component that explains Ο 75{\%} of the total BMD/BMC variation at the three sites. The results indicate that a major gene exists with a codominant effect that is responsible for Ο 16{\%} of the FS variation when adjusted for significant effects of sex, body weight and age. A significant genotype- x -sex- x -age interaction was found, which may explain Ο 14{\%} of the FS variation after adjusting for body weight. Testing of various models did not provide support for shared familial environmental effects but suggested the existence of residual polygenic effects, which may explain Ο 50{\%} of the FS variation when adjusting for sex, body weight and age. This study indicates a promising aspect of studies to identify a major gene for BMD/BMC variation in our pedigrees identified via extreme probands.",
author = "Deng, {H. W.} and G. Livshits and K. Yakovenko and Xu, {F. H.} and T. Conway and Davies, {K. M.} and H. Deng and Recker, {Robert R.}",
year = "2002",
month = "1",
doi = "10.1017/S0003480001008958",
language = "English",
volume = "66",
pages = "61--74",
journal = "Annals of Human Genetics",
issn = "0003-4800",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Evidence for a major gene for bone mineral-density/content in humandeng pedigrees identified via probands with extreme bone mineral density

AU - Deng, H. W.

AU - Livshits, G.

AU - Yakovenko, K.

AU - Xu, F. H.

AU - Conway, T.

AU - Davies, K. M.

AU - Deng, H.

AU - Recker, Robert R.

PY - 2002/1

Y1 - 2002/1

N2 - Bone mineral content (BMC) and/or bone mineral density (BMD, i.e. BMC scaled by bone size) are major determinants for osteoporosis, which is a serious health problem. The major determinant of variation in BMD/BMC is genetic. The few studies now available are inconsistent in the identification and/or even in the existence of major gene(s) for BMD/BMC. In 51 human pedigrees with 941 individuals (526 measured for phenotypes) identified via probands with extreme BMD values, we performed complex segregation analyses to test the existence of a genetic locus with a major effect on BMD/BMC variation. We analyzed BMD and BMC at the spine, hip and wrist jointly by employing, as the study phenotype, factor scores (FS) of the principle component that explains Ο 75% of the total BMD/BMC variation at the three sites. The results indicate that a major gene exists with a codominant effect that is responsible for Ο 16% of the FS variation when adjusted for significant effects of sex, body weight and age. A significant genotype- x -sex- x -age interaction was found, which may explain Ο 14% of the FS variation after adjusting for body weight. Testing of various models did not provide support for shared familial environmental effects but suggested the existence of residual polygenic effects, which may explain Ο 50% of the FS variation when adjusting for sex, body weight and age. This study indicates a promising aspect of studies to identify a major gene for BMD/BMC variation in our pedigrees identified via extreme probands.

AB - Bone mineral content (BMC) and/or bone mineral density (BMD, i.e. BMC scaled by bone size) are major determinants for osteoporosis, which is a serious health problem. The major determinant of variation in BMD/BMC is genetic. The few studies now available are inconsistent in the identification and/or even in the existence of major gene(s) for BMD/BMC. In 51 human pedigrees with 941 individuals (526 measured for phenotypes) identified via probands with extreme BMD values, we performed complex segregation analyses to test the existence of a genetic locus with a major effect on BMD/BMC variation. We analyzed BMD and BMC at the spine, hip and wrist jointly by employing, as the study phenotype, factor scores (FS) of the principle component that explains Ο 75% of the total BMD/BMC variation at the three sites. The results indicate that a major gene exists with a codominant effect that is responsible for Ο 16% of the FS variation when adjusted for significant effects of sex, body weight and age. A significant genotype- x -sex- x -age interaction was found, which may explain Ο 14% of the FS variation after adjusting for body weight. Testing of various models did not provide support for shared familial environmental effects but suggested the existence of residual polygenic effects, which may explain Ο 50% of the FS variation when adjusting for sex, body weight and age. This study indicates a promising aspect of studies to identify a major gene for BMD/BMC variation in our pedigrees identified via extreme probands.

UR - http://www.scopus.com/inward/record.url?scp=0036378851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036378851&partnerID=8YFLogxK

U2 - 10.1017/S0003480001008958

DO - 10.1017/S0003480001008958

M3 - Review article

VL - 66

SP - 61

EP - 74

JO - Annals of Human Genetics

JF - Annals of Human Genetics

SN - 0003-4800

IS - 1

ER -