A validation of the first genome-wide association study of calcaneus ultrasound parameters in the European Male Ageing Study

BMC Medical Genetics

Research Article

Gianni Forti¹  Margus Punab²  Stephen R Pye³  Kate L Holliday³  Joseph D Finn³  Delnaz Roshandel³  Wendy Thomson³  Terence W O'Neill³  Alan J Silman³  Neil Pendleton⁴  Judith E Adams⁵  Kate A Ward⁶  Krzysztof Kula⁷  Frederick C Wu⁸  Thang S Han⁹  Michael E Lean⁹  Felipe Casanueva^1,10  Gyorgy Bartfai^1,11  Ilpo T Huhtaniemi^1,12  Herman Borghs^1,13  Dirk Vanderschueren^1,14  Steven Boonen^1,15  Aleksander Giwercman^1,16 

[1] Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy;Andrology Unit, United Laboratories of Tartu University Clinics, Tartu, Estonia;Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK;Clinical Gerontology, The University of Manchester, Manchester Academic Health Science Centre, Hope Hospital, Salford, UK;Clinical Radiology, Manchester Royal Infirmary & Manchester Academic Health Science Centre, Manchester, UK;Clinical Radiology, Manchester Royal Infirmary & Manchester Academic Health Science Centre, Manchester, UK;MRC-Human Nutrition Research, Cambridge, UK;Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Lodz, Poland;Department of Endocrinology, Manchester Royal Infirmary, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK;Department of Human Nutrition, University of Glasgow, Glasgow, Scotland;Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago (CHUS), CIBER de Fisiopatologı'a Obesidad y Nutricion (CB06/03), Instituto Salud Carlos III, Santiago de Compostela, Spain;Department of Obstetrics, Gynaecology and Andrology, Albert Szent-Gyorgy Medical University, Szeged, Hungary;Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, London, UK;Leuven University Center for Metabolic Bone Diseases, Katholieke Universiteit Leuven, Leuven, Belgium;Leuven University Center for Metabolic Bone Diseases, Katholieke Universiteit Leuven, Leuven, Belgium;Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium;Leuven University Division of Geriatric Medicine, Katholieke Universiteit Leuven, Leuven, Belgium;Leuven University Center for Metabolic Bone Diseases, Katholieke Universiteit Leuven, Leuven, Belgium;Scanian Andrology Centre, Department of Urology, Malmö University Hospital, University of Lund, Lund, Sweden;

关键词: Bone Mineral Density;    Femoral Neck;    Minor Allele Frequency;    Framingham Study;    Broadband Ultrasound Attenuation;   

DOI  :  10.1186/1471-2350-12-19

 received in 2010-04-29, accepted in 2011-01-28,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundA number of single nucleotide polymorphisms (SNPs) have been associated with broadband ultrasound attenuation (BUA) and speed of sound (SOS) as measured by quantitative ultrasound (QUS) at the calcaneus in the Framingham 100K genome-wide association study (GWAS) but have not been validated in independent studies. The aim of this analysis was to determine if these SNPs are associated with QUS measurements assessed in a large independent population of European middle-aged and elderly men. The association between these SNPs and bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA) was also tested.MethodsMen aged 40-79 years (N = 2960) were recruited from population registers in seven European centres for participation in an observational study of male ageing, the European Male Ageing Study (EMAS). QUS at the calcaneus was measured in all subjects and blood was taken for genetic analysis. Lumbar spine (LS), femoral neck (FN) and total hip (TH) BMD were measured by DXA in a subsample of 620 men in two centres. SNPs associated with BUA or SOS in the Framingham study with p < 10-4 were selected and genotyped using SEQUENOM technology. Linear regression was used to test for the association between SNPs and standardised (SD) bone outcomes under an additive genetic model adjusting for centre. The same direction of effect and p < 0.05 indicated replication.ResultsThirty-four of 38 selected SNPs were successfully genotyped in 2377 men. Suggestive evidence of replication was observed for a single SNP, rs3754032, which was associated with a higher SOS (β(SD) = 0.07, p = 0.032) but not BUA (β(SD) = 0.02, p = 0.505) and is located in the 3'UTR of WDR77 (WD repeat domain 77) also known as androgen receptor cofactor p44. A single SNP, rs238358, was associated with BMD at the LS (β(SD) = -0.22, p = 0.014), FN (β(SD) = -0.31,p = 0.001) and TH (β(SD) = -0.36, p = 0.002) in a locus previously associated with LS BMD in large-scale GWAS, incorporating AKAP11 and RANKL.ConclusionsWe found suggestive evidence of association between a single SNP located in the 3'UTR of WDR77 with calcaneal ultrasound parameters. The majority of SNPs, associated with QUS parameters in the Framingham Study, were not replicated in an independent population sample of European men.

【 授权许可】

Unknown   
© Roshandel et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.