Analysis of SNP-SNP interactions and bone quantitative ultrasound parameter in early adulthood.

Published on Oct 3, 2017in BMC Medical Genetics1.585
· DOI :10.1186/S12881-017-0468-6
María Correa-Rodríguez13
Estimated H-index: 13
(UGR: University of Granada),
Sebastien Viatte17
Estimated H-index: 17
(MAHSC: Manchester Academic Health Science Centre)
+ 3 AuthorsGisela Orozco31
Estimated H-index: 31
(MAHSC: Manchester Academic Health Science Centre)
Osteoporosis individual susceptibility is determined by the interaction of multiple genetic variants and environmental factors. The aim of this study was to conduct SNP-SNP interaction analyses in candidate genes influencing heel quantitative ultrasound (QUS) parameter in early adulthood to identify novel insights into the mechanism of disease. The study population included 575 healthy subjects (mean age 20.41; SD 2.36). To assess bone mass QUS was performed to determine Broadband ultrasound attenuation (BUA, dB/MHz). A total of 32 SNPs mapping to loci that have been characterized as genetic markers for QUS and/or BMD parameters were selected as genetic markers in this study. The association of all possible SNP pairs with QUS was assessed by linear regression and a SNP-SNP interaction was defined as a significant departure from additive effects. The pairwise SNP-SNP analysis showed multiple interactions. The interaction comprising SNPs rs9340799 and rs3736228 that map in the ESR1 and LRP5 genes respectively, revealed the lowest p value after adjusting for confounding factors (p-value = 0.001, β (95% CI) = 14.289 (5.548, 23.029). In addition, our model reported others such as TMEM135-WNT16 (p = 0.007, β(95%CI) = 9.101 (2.498, 15.704), ESR1-DKK1 (p = 0.012, β(95%CI) = 13.641 (2.959, 24.322) or OPG-LRP5 (p = 0.012, β(95%CI) = 8.724 (1.936, 15.512). However, none of the detected interactions remain significant considering the Bonferroni significance threshold for multiple testing (p<0.0001). Our analysis of SNP-SNP interaction in candidate genes of QUS in Caucasian young adults reveal several interactions, especially between ESR1 and LRP5 genes, that did not reach statistical significance. Although our results do not support a relevant genetic contribution of SNP-SNP epistatic interactions to QUS in young adults, further studies in larger independent populations would be necessary to support these preliminary findings.
#1María Correa-Rodríguez (UGR: University of Granada)H-Index: 13
#2Jacqueline Schmidt-RioValle (UGR: University of Granada)H-Index: 14
Last. Blanca Rueda-Medina (UGR: University of Granada)H-Index: 8
view all 3 authors...
The aim of the present study was to investigate the possible influence of low-density lipoprotein receptor-related protein 5 (LRP5) and sclerostin (SOST) genes as genetic factors contributing to calcaneal quantitative ultrasound (QUS) and body composition variables in a population of young Caucasian adults. The study population comprised a total of 575 individuals (mean age 20.41years; SD 2.36) whose bone mass was assessed through QUS to determine broadband ultrasound attenuation (BUA, dB/MHz). ...
2 CitationsSource
#1María Correa-Rodríguez (UGR: University of Granada)H-Index: 13
#2J. Schmidt Río-Valle (UGR: University of Granada)H-Index: 4
Last. Blanca Rueda-Medina (UGR: University of Granada)H-Index: 8
view all 3 authors...
Summary Bone mineral content is influenced by genetic factors. We investigated the role of WNT16 in bone properties determined using quantitative ultrasound (QUS) on young adults. Three WNT16 genetic markers (rs2908007, rs2908004, and rs2707466) were found to have a significant association with the broadband ultrasound attenuation (BUA) measurement, suggesting that WNT16 influences bone mass in young adults.
8 CitationsSource
#1Ganna ChornokurH-Index: 17
#2Hui-Yi LinH-Index: 20
Last. Catherine M. PhelanH-Index: 47
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© 2015 Chornokur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage...
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#1Chin Lin (NDMC: National Defense Medical Center)H-Index: 13
#2Chi-Ming Chu (NDMC: National Defense Medical Center)H-Index: 14
Last. Sui-Lung Su (NDMC: National Defense Medical Center)H-Index: 12
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Extensive genetic studies have identified a large number of causal genetic variations in many human phenotypes; however, these could not completely explain heritability in complex diseases. Some researchers have proposed that the “missing heritability” may be attributable to gene–gene and gene–environment interactions. Because there are billions of potential interaction combinations, the statistical power of a single study is often ineffective in detecting these interactions. Meta-analysis is a ...
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#1Eugene McCloskey (Northern General Hospital)H-Index: 105
#2John A. Kanis (University of Sheffield)H-Index: 149
Last. Helena Johansson (University of Sheffield)H-Index: 77
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Summary The relationship between bone quantitative ultrasound (QUS) and fracture risk was estimated in an individual level data meta-analysis of 9 prospective studies of 46,124 individuals and 3018 incident fractures. Low QUS is associated with an increase in fracture risk, including hip fracture. The association with osteoporotic fracture decreases with time.
49 CitationsSource
#1Alireza Moayyeri (University of Cambridge)H-Index: 34
#2Yi-Hsiang Hsu (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 43
Last. Stephen Kaptoge (University of Cambridge)H-Index: 57
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Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independ...
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#1Tie-Lin Yang (Xi'an Jiaotong University)H-Index: 28
#2Yan Guo (Xi'an Jiaotong University)H-Index: 56
Last. Hong-Wen Deng (Tulane University)H-Index: 28
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Osteoporosis is characterized by low bone mineral density (BMD), a highly heritable trait that is determined, in part, by the actions and interactions of multiple genes. Although an increasing number of genes have been identified to have independent effects on BMD, few studies have been performed to identify genes that interact with one another to affect BMD. In this study, we performed gene-gene interaction analyses in selected candidate genes in individuals with extremely high versus low hip B...
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#1Daniel L. Koller (IU: Indiana University)H-Index: 51
#2Hou-Feng Zheng (McGill University)H-Index: 29
Last. Tatiana Foroud (IU: Indiana University)H-Index: 130
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Previous genome-wide association studies (GWAS) have identified common variants in genes associated with variation in bone mineral density (BMD), although most have been carried out in combined samples of older women and men. Meta-analyses of these results have identified numerous single-nucleotide polymorphisms (SNPs) of modest effect at genome-wide significance levels in genes involved in both bone formation and resorption, as well as other pathways. We performed a meta-analysis restricted to ...
71 CitationsSource
#1Carmen García-Ibarbia (UC: University of Cantabria)H-Index: 11
Last. José A. Riancho (UC: University of Cantabria)H-Index: 46
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Summary Two missense polymorphisms of WNT16 were associated with hip bone mineral density (BMD), the buckling ratio of the femoral neck, calcaneal ultrasound and hip fractures in individuals under 80 years of age. These results confirm the association of the WNT16 gene with bone mass and osteoporotic fractures.
43 CitationsSource
#1Franklin D. Shuler (Marshall University)H-Index: 20
#2Jacob Conjeski MdH-Index: 3
Last. Jonathon SalavaH-Index: 1
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: Fracture prevention is a critical component of managing osteoporosis, which is not longer defined by T-score alone. The internationally validated World Health Organization Fracture Risk Assessment Tool (FRAX) provides the clinician a state-of-the-art tool for predicting patients at greatest risk for fracture. The FRAX tool takes into account country, bone mineral density of the hip (when available), age, sex, and 8 clinical risk factors to calculate the 10-year probability of a major osteoporo...
28 CitationsSource
Cited By2
#1Nicola Rares Franco (Ghent University Hospital)
#1Nicola Rares Franco (Ghent University Hospital)H-Index: 1
Last. Tiziana RancatiH-Index: 27
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AIM To identify the effect of single nucleotide polymorphism (SNP) interactions on the risk of toxicity following radiotherapy (RT) for prostate cancer (PCa) and propose a new method for polygenic risk score incorporating SNP-SNP interactions (PRSi). MATERIALS AND METHODS Analysis included the REQUITE PCa cohort that received external beam RT and was followed for 2 years. Late toxicity endpoints were: rectal bleeding, urinary frequency, haematuria, nocturia, decreased urinary stream. Among 43 li...
#1Vladimira Mondockova (University of Constantine the Philosopher)H-Index: 1
#2Mária Adamkovičová (University of Constantine the Philosopher)H-Index: 7
Last. Radoslav Omelka (University of Constantine the Philosopher)H-Index: 12
view all 8 authors...
Background The study investigated the associations of rs9340799:A > G (XbaI) and rs2234693:T > C (PvuII) polymorphisms in the estrogen receptor 1 gene (ESR1) with femoral neck (BMD-FN) and lumbar spine bone mineral density (BMD-LS), biochemical markers of bone turnover, calcium and phosphate levels, fracture prevalence, and a response to two types of anti-osteoporotic therapy in postmenopausal women from southern Slovakia.
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