INTRODUCTION: Areal bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) measures are correlated, and both traits predict osteoporotic fracture risk independently. However, few studies have examined whether common genetic effects (i.e., pleiotropy) exist between these traits in extended families. In this study, we estimated the additive genetic correlation and random environmental correlation between BMD measured at various skeletal sites and calcaneal QUS measures. METHODS: Our sample included 537 adults (251 men and 286 women) from 110 families participating in the Fels Longitudinal Study. Total hip, femoral neck, lumbar spine, and total body BMD were measured using dual energy X-ray absorptiometry. Three measures of calcaneal structure--broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI)--were collected from the non-dominant heel using the Sahara sonometer. Applying a variance components-based maximum likelihood method, we estimated the heritability of each trait and estimated the genetic and environmental correlations between the different BMD and QUS measures. RESULTS: Heritability estimates were significant for all measures of BMD and QUS ranging from 0.55 to 0.78. Significant non-zero genetic correlations were found between the different BMD and QUS measures. All genetic correlations were also significantly different from 1. Genetic correlations between total hip BMD and each of the QUS measures were 0.63 with BUA, 0.50 with SOS, and 0.56 with QUI. For femoral neck BMD, genetic correlations were similar to those between total hip BMD and QUS measures. Genetic correlations between BMD of the lumbar spine and QUS measures ranged from 0.34 to 0.38, and those between total body BMD and QUS measures, from 0.51 to 0.54. In contrast, all random environmental correlations were not significantly different from zero. CONCLUSION: This study demonstrates that BMD and calcaneal QUS measures among healthy men and women are significantly heritable and are, in part, jointly influenced by a common set of underlying genes. Additionally, this study also provides evidence for a unique set of genes that independently influences each individual trait.
INTRODUCTION: Areal bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) measures are correlated, and both traits predict osteoporotic fracture risk independently. However, few studies have examined whether common genetic effects (i.e., pleiotropy) exist between these traits in extended families. In this study, we estimated the additive genetic correlation and random environmental correlation between BMD measured at various skeletal sites and calcaneal QUS measures. METHODS: Our sample included 537 adults (251 men and 286 women) from 110 families participating in the Fels Longitudinal Study. Total hip, femoral neck, lumbar spine, and total body BMD were measured using dual energy X-ray absorptiometry. Three measures of calcaneal structure--broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI)--were collected from the non-dominant heel using the Sahara sonometer. Applying a variance components-based maximum likelihood method, we estimated the heritability of each trait and estimated the genetic and environmental correlations between the different BMD and QUS measures. RESULTS: Heritability estimates were significant for all measures of BMD and QUS ranging from 0.55 to 0.78. Significant non-zero genetic correlations were found between the different BMD and QUS measures. All genetic correlations were also significantly different from 1. Genetic correlations between total hip BMD and each of the QUS measures were 0.63 with BUA, 0.50 with SOS, and 0.56 with QUI. For femoral neck BMD, genetic correlations were similar to those between total hip BMD and QUS measures. Genetic correlations between BMD of the lumbar spine and QUS measures ranged from 0.34 to 0.38, and those between total body BMD and QUS measures, from 0.51 to 0.54. In contrast, all random environmental correlations were not significantly different from zero. CONCLUSION: This study demonstrates that BMD and calcaneal QUS measures among healthy men and women are significantly heritable and are, in part, jointly influenced by a common set of underlying genes. Additionally, this study also provides evidence for a unique set of genes that independently influences each individual trait.
Authors: Claus C Glüer; Richard Eastell; David M Reid; Dieter Felsenberg; Christian Roux; Reinhard Barkmann; Wolfram Timm; Tilo Blenk; Gabi Armbrecht; Alison Stewart; Jackie Clowes; Friederike E Thomasius; Sami Kolta Journal: J Bone Miner Res Date: 2004-03-01 Impact factor: 6.741
Authors: Miryoung Lee; Stefan A Czerwinski; Audrey C Choh; Bradford Towne; Ellen W Demerath; Wm Cameron Chumlea; Shumei S Sun; Roger M Siervogel Journal: Bone Date: 2004-11 Impact factor: 4.398
Authors: M Lee; R W Nahhas; A C Choh; E W Demerath; D L Duren; W C Chumlea; R J Sherwood; B Towne; R M Siervogel; S A Czerwinski Journal: Osteoporos Int Date: 2010-10-26 Impact factor: 4.507
Authors: Dana L Duren; Richard J Sherwood; Audrey C Choh; Stefan A Czerwinski; Wm Cameron Chumlea; Miryoung Lee; Shumei S Sun; Ellen W Demerath; Roger M Siervogel; Bradford Towne Journal: Bone Date: 2006-10-23 Impact factor: 4.398
Authors: Alireza Moayyeri; Yi-Hsiang Hsu; David Karasik; Karol Estrada; Su-Mei Xiao; Carrie Nielson; Priya Srikanth; Sylvie Giroux; Scott G Wilson; Hou-Feng Zheng; Albert V Smith; Stephen R Pye; Paul J Leo; Alexander Teumer; Joo-Yeon Hwang; Claes Ohlsson; Fiona McGuigan; Ryan L Minster; Caroline Hayward; José M Olmos; Leo-Pekka Lyytikäinen; Joshua R Lewis; Karin M A Swart; Laura Masi; Chris Oldmeadow; Elizabeth G Holliday; Sulin Cheng; Natasja M van Schoor; Nicholas C Harvey; Marcin Kruk; Fabiola del Greco M; Wilmar Igl; Olivia Trummer; Efi Grigoriou; Robert Luben; Ching-Ti Liu; Yanhua Zhou; Ling Oei; Carolina Medina-Gomez; Joseph Zmuda; Greg Tranah; Suzanne J Brown; Frances M Williams; Nicole Soranzo; Johanna Jakobsdottir; Kristin Siggeirsdottir; Kate L Holliday; Anke Hannemann; Min Jin Go; Melissa Garcia; Ozren Polasek; Marika Laaksonen; Kun Zhu; Anke W Enneman; Mark McEvoy; Roseanne Peel; Pak Chung Sham; Maciej Jaworski; Åsa Johansson; Andrew A Hicks; Pawel Pludowski; Rodney Scott; Rosalie A M Dhonukshe-Rutten; Nathalie van der Velde; Mika Kähönen; Jorma S Viikari; Harri Sievänen; Olli T Raitakari; Jesús González-Macías; Jose L Hernández; Dan Mellström; Osten Ljunggren; Yoon Shin Cho; Uwe Völker; Matthias Nauck; Georg Homuth; Henry Völzke; Robin Haring; Matthew A Brown; Eugene McCloskey; Geoffrey C Nicholson; Richard Eastell; John A Eisman; Graeme Jones; Ian R Reid; Elaine M Dennison; John Wark; Steven Boonen; Dirk Vanderschueren; Frederick C W Wu; Thor Aspelund; J Brent Richards; Doug Bauer; Albert Hofman; Kay-Tee Khaw; George Dedoussis; Barbara Obermayer-Pietsch; Ulf Gyllensten; Peter P Pramstaller; Roman S Lorenc; Cyrus Cooper; Annie Wai Chee Kung; Paul Lips; Markku Alen; John Attia; Maria Luisa Brandi; Lisette C P G M de Groot; Terho Lehtimäki; José A Riancho; Harry Campbell; Yongmei Liu; Tamara B Harris; Kristina Akesson; Magnus Karlsson; Jong-Young Lee; Henri Wallaschofski; Emma L Duncan; Terence W O'Neill; Vilmundur Gudnason; Timothy D Spector; François Rousseau; Eric Orwoll; Steven R Cummings; Nick J Wareham; Fernando Rivadeneira; Andre G Uitterlinden; Richard L Prince; Douglas P Kiel; Jonathan Reeve; Stephen K Kaptoge Journal: Hum Mol Genet Date: 2014-01-14 Impact factor: 6.150
Authors: John P Kemp; John A Morris; Carolina Medina-Gomez; Vincenzo Forgetta; Nicole M Warrington; Scott E Youlten; Jie Zheng; Celia L Gregson; Elin Grundberg; Katerina Trajanoska; John G Logan; Andrea S Pollard; Penny C Sparkes; Elena J Ghirardello; Rebecca Allen; Victoria D Leitch; Natalie C Butterfield; Davide Komla-Ebri; Anne-Tounsia Adoum; Katharine F Curry; Jacqueline K White; Fiona Kussy; Keelin M Greenlaw; Changjiang Xu; Nicholas C Harvey; Cyrus Cooper; David J Adams; Celia M T Greenwood; Matthew T Maurano; Stephen Kaptoge; Fernando Rivadeneira; Jonathan H Tobias; Peter I Croucher; Cheryl L Ackert-Bicknell; J H Duncan Bassett; Graham R Williams; J Brent Richards; David M Evans Journal: Nat Genet Date: 2017-09-04 Impact factor: 38.330
Authors: Jie Zheng; Monika Frysz; John P Kemp; David M Evans; George Davey Smith; Jonathan H Tobias Journal: Front Endocrinol (Lausanne) Date: 2019-11-21 Impact factor: 5.555