Identification of novel genetic loci for osteoporosis and/or rheumatoid arthritis using cFDR approach

Autor: Zeng-Xing Ao, Jie Shen, Xia-Fang Wang, Rou Zhou, Yuan-Cheng Chen, Chun-Ping Zeng, Xiao Chun Bai, Hong-Wen Deng, Jun-Min Lu, Xu Lin, Ding-You Li, Lin-Ping Peng, Jonathan Greenbaum
Rok vydání: 2017
Předmět:
0301 basic medicine
False discovery rate
Gene Expression
lcsh:Medicine
Genome-wide association study
Bioinformatics
Arthritis
Rheumatoid
Major Histocompatibility Complex
Mathematical and Statistical Techniques
0302 clinical medicine
Risk Factors
Medicine and Health Sciences
lcsh:Science
Genetics
Multidisciplinary
Genomics
3. Good health
Phenotypes
030220 oncology & carcinogenesis
Rheumatoid arthritis
Meta-analysis
Physical Sciences
Statistics (Mathematics)
Research Article
Immunology
Rheumatoid Arthritis
Single-nucleotide polymorphism
Biology
Genome Complexity
Research and Analysis Methods
Major histocompatibility complex
Polymorphism
Single Nucleotide
Autoimmune Diseases
03 medical and health sciences
Rheumatology
Genome-Wide Association Studies
medicine
Humans
Genetic Predisposition to Disease
Gene Regulation
Statistical Methods
Risk factor
Arthritis
lcsh:R
Biology and Life Sciences
Computational Biology
Human Genetics
Genome Analysis
medicine.disease
Introns
030104 developmental biology
Genetic Loci
biology.protein
Osteoporosis
Clinical Immunology
lcsh:Q
Clinical Medicine
Mathematics
Genome-Wide Association Study
Meta-Analysis
Zdroj: PLoS ONE, Vol 12, Iss 8, p e0183842 (2017)
PLoS ONE
ISSN: 1932-6203
Popis: There are co-morbidity between osteoporosis (OP) and rheumatoid arthritis (RA). Some genetic risk factors have been identified for these two phenotypes respectively in previous research; however, they accounted for only a small portion of the underlying total genetic variances. Here, we sought to identify additional common genetic loci associated with OP and/or RA. The conditional false discovery rate (cFDR) approach allows detection of additional genetic factors (those respective ones as well as common pleiotropic ones) for the two associated phenotypes. We collected and analyzed summary statistics provided by large, multi-center GWAS studies of FNK (femoral neck) BMD (a major risk factor for osteoporosis) (n = 53,236) and RA (n = 80,799). The conditional quantile-quantile (Q-Q) plots can assess the enrichment of SNPs related to FNK BMD and RA, respectively. Furthermore, we identified shared loci between FNK BMD and RA using conjunction cFDR (ccFDR). We found strong enrichment of p-values in FNK BMD when conditional Q-Q was done on RA and vice versa. We identified 30 novel OP-RA associated pleiotropic loci that have not been reported in previous OP or RA GWAS, 18 of which located in the MHC (major histocompatibility complex) region previously reported to play an important role in immune system and bone health. We identified some specific novel polygenic factors for OP and RA respectively, and identified 30 novel OP-RA associated pleiotropic loci. These discovery findings may offer novel pathobiological insights, and suggest new targets and pathways for drug development in OP and RA patients.
Databáze: OpenAIRE
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