Identifying potentially common genes between dyslipidemia and osteoporosis using novel analytical approaches

Lin, Xu; Peng, Cheng; Greenbaum, Jonathan; Li, Zhangfang; Wu, Kai-Kai; Ao, Zeng-Xin; Zhang, Tong; Shen, Jie; Deng, Hong‐Wen

doi:10.1007/s00438-017-1414-1

Cited by 14 publications

(9 citation statements)

References 53 publications

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“…Among adults, a small male predominance of HPI-related outcomes has been found in a meta-analysis based on 169 studies (OR 1.12, 95% CI: 1.09, 1.15) [ 407 ]. Shared genetic basis underlying OP and a variety of HPI-related chronic extra-gastroduodenal diseases (CAD, DM, dyslipidemia) has been reported [ 408 , 409 , 410 , 411 , 412 , 413 , 414 , 415 , 416 , 417 , 418 , 419 ]. The shared biology and bi-(multi-)directional links between OP and HPI-associated chronic diseases apply particularly to CVD, CKD, CLD, DM and neurodegenerative diseases; these disorders are interrelated and often accompanied by OP/OF [ 420 , 421 , 422 , 423 , 424 , 425 , 426 , 427 , 428 , 429 , 430 ], and the risk of OP/OF increases when two or more HPI-associated chronic diseases are present.…”

Section: Hpi-associated Chronic Extra-gastroduodenal Diseases Medmentioning

confidence: 99%

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

Fisher

Smith

2020

JCM

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Osteoporosis (OP) and osteoporotic fractures (OFs) are common multifactorial and heterogenic disorders of increasing incidence. Helicobacter pylori (H.p.) colonizes the stomach approximately in half of the world’s population, causes gastroduodenal diseases and is prevalent in numerous extra-digestive diseases known to be associated with OP/OF. The studies regarding relationship between H.p. infection (HPI) and OP/OFs are inconsistent. The current review summarizes the relevant literature on the potential role of HPI in OP, falls and OFs and highlights the reasons for controversies in the publications. In the first section, after a brief overview of HPI biological features, we analyze the studies evaluating the association of HPI and bone status. The second part includes data on the prevalence of OP/OFs in HPI-induced gastroduodenal diseases (peptic ulcer, chronic/atrophic gastritis and cancer) and the effects of acid-suppressive drugs. In the next section, we discuss the possible contribution of HPI-associated extra-digestive diseases and medications to OP/OF, focusing on conditions affecting both bone homeostasis and predisposing to falls. In the last section, we describe clinical implications of accumulated data on HPI as a co-factor of OP/OF and present a feasible five-step algorithm for OP/OF risk assessment and management in regard to HPI, emphasizing the importance of an integrative (but differentiated) holistic approach. Increased awareness about the consequences of HPI linked to OP/OF can aid early detection and management. Further research on the HPI–OP/OF relationship is needed to close current knowledge gaps and improve clinical management of both OP/OF and HPI-related disorders.

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Section: Hpi-associated Chronic Extra-gastroduodenal Diseases Medmentioning

confidence: 99%

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

Fisher

Smith

2020

JCM

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“…Bone mineral density (BMD) and serum total cholesterol (TC) are among two of the most extensively studied clinically-oriented phenotypes, associated with the two of the most common polygenic age-related pathologies, osteoporosis (OP) and cardiovascular disease (CVD). There is an abundant literature showing correlation between these biomarkers and possible mechanisms underlying it [1–4], although the views and the data remain controversial [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…In particular, it is unclear whether BMD and lipids are related due to pleiotropic genetic influences or through direct causal influence of one on the other. One of the most convincing studies employed conditional false-discovery rate and other approaches on large genome-wide association studies (GWAS) of BMD and cholesterol and found pleiotropy among the significant single nucleotide polymorphisms (SNPs) for the two phenotypes [4]. A comprehensive GWAS in a combined sample of the TwinsUK study and the Cooperative Health Research in the Region of Augsburg (KORA) study including nearly 8000 individuals identified 145 SNP associations with over 400 blood metabolites [7].…”

Section: Introductionmentioning

confidence: 99%

The analysis of causal relationships between blood lipid levels and BMD

et al. 2019

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Bone mineral density (BMD) and lipid levels are two of the most extensively studied risk factors for common diseases of aging, such as cardiovascular disease (CVD) and osteoporosis (OP). These two risk factors are also correlated with each other, but little is known about the molecular mechanisms behind this correlation. Recent studies revealed that circulating levels of several metabolites involved in the biosynthesis of androsterone correlate significantly with BMD and have the capacity to affect cholesterol and lipids levels. A main aim of the present study was to investigate the hypothesis that androsterone-related metabolites could provide a link between CVD and OP, as a common cause of lipid levels and BMD. The present study employed data from the NIHR BRC TwinsUK BioResource, comprising 1909 and 1994 monozygotic and dizygotic twin pairs, respectively, to address the causal relationships among BMD and lipids, and their associated metabolites, using reciprocal causation twin modelling, as well as Mendelian randomization (MR) using large publicly-available GWAS datasets on lipids and BMD, in conjunction with TwinsUK metabolite data. While results involving the twin modelling and MR analyses with metabolites were unable to establish a causal link between metabolite levels and either lipids or BMD, MR analyses of BMD and lipids suggest that lipid levels have a causal impact on BMD, which is consistent with findings from clinical trials of lipid-lowering drugs, which have also increased BMD.

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“…First, two GWAS datasets were combined and 8,285,296 common SNPs with summary statistics remained for both CAD and BW phenotypes. Then, we performed LD-based pruning (r 2 ≤ 0.2) using HapMap III genotypes as a reference, and the SNP of the pair with longer allele frequency was retained [ 31 , 68 ]. After merging and pruning, 141,779 variants were prepared for further analysis.…”

Section: Methodsmentioning

confidence: 99%

Identification of novel SNPs associated with coronary artery disease and birth weight using a pleiotropic cFDR method

Lin

Li³

et al. 2020

Aging

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Objectives: Clinical and epidemiological findings indicate an association between coronary artery disease (CAD) and low birth weight (BW). However, the mechanisms underlying this relationship are largely unknown. Here, we aimed to identify novel single-nucleotide polymorphisms (SNPs) associated with CAD, BW, and their shared pleiotropic loci, and to detect the potential causal relationship between CAD and BW. Methods: We first applied a genetic pleiotropic conditional false discovery rate (cFDR) method to two independent genome-wide association studies (GWAS) summary statistics of CAD and BW to estimate the pleiotropic enrichment between them. Then, bi-directional Mendelian randomization (MR) analyses were performed to clarify the causal association between these two traits. Results: By incorporating related traits into a conditional analysis framework, we observed the significant pleiotropic enrichment between CAD and BW. By applying the cFDR level of 0.05, 109 variants were detected for CAD, 203 for BW, and 26 pleiotropic variants for both traits. We identified 11 CAD- and/or BW-associated SNPs that showed more than three of the metabolic quantitative trait loci (metaQTL), protein QTL (pQTL), methylation QTL (meQTL), or expression QTL (eQTL) effects. The pleiotropic SNP rs10774625, located at ATXN2, showed metaQTL, pQTL, meQTL, and eQTL effects simultaneously. Using the bi-directional MR approach, we found a negative association from BW to CAD (odds ratio [OR] = 0.68, 95% confidence interval [CI]: 0.59 to 0.80, p = 1.57× 10 -6 ). Conclusion: We identified several pleiotropic loci between CAD and BW by leveraging GWAS results of related phenotypes and identified a potential causal relationship from BW to CAD. Our findings provide novel insights into the shared biological mechanisms and overlapping genetic heritability between CAD and BW.

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Identifying potentially common genes between dyslipidemia and osteoporosis using novel analytical approaches

Cited by 14 publications

References 53 publications

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

The analysis of causal relationships between blood lipid levels and BMD

Identification of novel SNPs associated with coronary artery disease and birth weight using a pleiotropic cFDR method

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