Epigenome Wide DNA Methylation Study for Osteoporosis Risk

Osteoporosis is characterized by low bone mineral density (BMD). The advancement of high-throughput technologies and integrative approaches provided an opportunity for deciphering the mechanisms underlying osteoporosis. In this study, we generated genomic (from whole blood DNA), transcriptomic and methylomic (from peripheral blood monocytes, PBMs), and serum metabolomic datasets from 143 premenopausal Caucasian females aged 25-40 years, including 74 with relatively high hip BMD (Z scores ≥ 0.8) and 69 with relatively low hip BMD (Z scores ≤ -0.8). The BMD Z score was defined as the number of standard deviations a subject's BMD differed from the mean BMD of their age-, gender-, and ethnicity-matched population. We identified differentially methylated CpG sites (DMCs) in peripheral blood monocytes (PBMs) at the whole methylome level between premenopausal women with high BMD and those with low BMD and deciphered how the DMCs influence the BMD variation through affecting the expression of the relevant genes. We also performed differential gene expression and metabolic analysis to assess their biological interaction and causal mechanisms. Our study provided novel insights into the pathogenesis of osteoporosis.]]>
Individuals must meet the following inclusion criteria to be eligible to participate in the study: 1) Caucasian females 2) Aged 20-40 years 3) With at least one intact ovary 4) Hip BMD Z-score ≥ 0.8 or ≤ -0.8 We adopted the following exclusion criteria to minimize non-genetic influence on bone mass variation, so as to empirically enhance the chance to detect individual genetic factors for bone mass. 1) Female subjects who are, or could be pregnant; 2) Serious residuals from cerebral vascular disease; 3) Diabetes mellitus, except for those controlled under medication; 4) Chronic renal failure; 5) Chronic liver failure; 6) Alcohol abuses as defined by those who drink alcohol regularly and cannot control themselves and get drunk at least once a week; 7) Chronic obstructive pulmonary disease (COPD); 8) Corticosteroid therapy at therapeutic levels for more than 6 months duration; 9) Treatment with anticonvulsant therapy for more than 6 months duration; 10) Other metabolic or inherited bone diseases including hyper- or hypoparathyroidism, Paget's disease, osteomalacia, osteogenisis imperfecta, and hypochondrogenesis; 11) Rheumatoid arthritis, except for minor cases that involve only hand joint and wrist; 12) Chronic gastrointestinal disease including celiac disease, postygastrectomy, Crohn's disease, ulcerative colitis, liver transplant, and cirrhosis; Given that PBMs are essential component of the immune system, we adopted the following additional exclusion criteria in order to minimize the effect of diseases or conditions, which may potentially lead to the transcriptomic and epigenomic profiling changes: 1. Autoimmune or autoimmune-related diseases: systemic lupus erythematosus, multiple sclerosis, Graves disease, Hashimoto's thyroiditis, myasthenia gravis, Addison's disease, dermatomyositis, Sjogren's syndrome, Reiter's syndrome. 2. Immune-deficiency conditions: AIDS, severe malnutrition, splenectomy, ataxia-telangiectasia, DiGeorge syndrome, Chediak-Higashi syndrome, job syndrome, leukocyte adhesion defects, panhypogammaglobulinemia, selective deficiency of IgA, combined immunodeficiency disease, Wiscott-Aldrich syndrome. 3. Haematopoietic and lymphoreticular malignancies: leukaemias, lymphomas (Hodgkin's disease, non-Hodgkin's disease), myeloma, Waldenstrőm's macroglobulinaemia, heavy chain disease, leukemic reticuloendotheliosis, mastocytosis, malignant histiocytosis. 4. Other diseases: influenza (within one week of recruitment), active periods of asthma. ]]>