A road map for understanding molecular and genetic determinants of osteoporosis

被引:383
作者
Yang, Tie-Lin [1 ]
Shen, Hui [2 ]
Liu, Anqi [2 ]
Dong, Shan-Shan [1 ]
Zhang, Lei [3 ]
Deng, Fei-Yan [3 ]
Zhao, Qi [4 ]
Deng, Hong-Wen [2 ,5 ]
机构
[1] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian, Peoples R China
[2] Tulane Univ, Dept Global Biostat & Data Sci, Ctr Bioinformat & Genom, New Orleans, LA 70118 USA
[3] Soochow Univ, Coll Med, Sch Publ Hlth, Ctr Genet Epidemiol & Genom, Suzhou, Jiangsu, Peoples R China
[4] Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Prevent Med, Memphis, TN 38163 USA
[5] Cent South Univ, Sch Basic Med Sci, Changsha, Peoples R China
关键词
BONE-MINERAL DENSITY; GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR-ALPHA; INTEGRATIVE ANALYSIS; DNA METHYLATION; SUSCEPTIBILITY GENE; PROTEOMIC ANALYSIS; SERUM SCLEROSTIN; FRACTURE RISK; BMD;
D O I
10.1038/s41574-019-0282-7
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Osteoporosis is a highly prevalent disorder characterized by low bone mineral density and an increased risk of fracture, termed osteoporotic fracture. Notably, bone mineral density, osteoporosis and osteoporotic fracture are highly heritable; however, determining the genetic architecture, and especially the underlying genomic and molecular mechanisms, of osteoporosis in vivo in humans is still challenging. In addition to susceptibility loci identified in genome-wide association studies, advances in various omics technologies, including genomics, transcriptomics, epigenomics, proteomics and metabolomics, have all been applied to dissect the pathogenesis of osteoporosis. However, each technology individually cannot capture the entire view of the disease pathology and thus fails to comprehensively identify the underlying pathological molecular mechanisms, especially the regulatory and signalling mechanisms. A change to the status quo calls for integrative multi-omics and inter-omics analyses with approaches in 'systems genetics and genomics'. In this Review, we highlight findings from genome-wide association studies and studies using various omics technologies individually to identify mechanisms of osteoporosis. Furthermore, we summarize current studies of data integration to understand, diagnose and inform the treatment of osteoporosis. The integration of multiple technologies will provide a road map to illuminate the complex pathogenesis of osteoporosis, especially from molecular functional aspects, in vivo in humans. In this Review, the authors highlight findings from genome-wide association studies and studies using various omics technologies individually to identify mechanisms of osteoporosis, which is a highly heritable condition. They also summarize current studies of data integration to understand, diagnose and inform the treatment of osteoporosis.
引用
收藏
页码:91 / 103
页数:13
相关论文
共 157 条
[1]
Dissecting the Genetics of Osteoporosis using Systems Approaches [J].
Al-Barghouthi, Basel M. ;
Farber, Charles R. .
TRENDS IN GENETICS, 2019, 35 (01) :55-67
[2]
[Anonymous], 2018, Broken bones, broken lives: a roadmap to solve the fragility fracture crisis in Europe
[3]
[Anonymous], 1858, NYDTr
[4]
[Anonymous], 2016, SCI REP
[5]
Serum Sclerostin and Risk of Hip Fracture in Older Caucasian Women [J].
Arasu, Aarthi ;
Cawthon, Peggy M. ;
Lui, Li-Yung ;
Do, Thy P. ;
Arora, Puneet S. ;
Cauley, Jane A. ;
Ensrud, Kristine E. ;
Cummings, Steven R. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 97 (06) :2027-2032
[6]
Prospects of Fine-Mapping Trait-Associated Genomic Regions by Using Summary Statistics from Genome-wide Association Studies [J].
Benner, Christian ;
Havulinna, Aki S. ;
Jarvelin, Marjo-Riitta ;
Salomaa, Veikko ;
Ripatti, Samuli ;
Pirinen, Matti .
AMERICAN JOURNAL OF HUMAN GENETICS, 2017, 101 (04) :539-551
[7]
FINEMAP: efficient variable selection using summary data from genome-wide association studies [J].
Benner, Christian ;
Spencer, Chris C. A. ;
Havulinna, Aki S. ;
Salomaa, Veikko ;
Ripatti, Samuli ;
Pirinen, Matti .
BIOINFORMATICS, 2016, 32 (10) :1493-1501
[8]
Serum biomarker profile associated with high bone turnover and BMD in postmenopausal women [J].
Bhattacharyya, Sudeepa ;
Siegel, Eric R. ;
Achenbach, Sara J. ;
Khosla, Sundeep ;
Suva, Larry J. .
JOURNAL OF BONE AND MINERAL RESEARCH, 2008, 23 (07) :1106-1117
[9]
Annotation of functional variation in personal genomes using RegulomeDB [J].
Boyle, Alan P. ;
Hong, Eurie L. ;
Hariharan, Manoj ;
Cheng, Yong ;
Schaub, Marc A. ;
Kasowski, Maya ;
Karczewski, Konrad J. ;
Park, Julie ;
Hitz, Benjamin C. ;
Weng, Shuai ;
Cherry, J. Michael ;
Snyder, Michael .
GENOME RESEARCH, 2012, 22 (09) :1790-1797
[10]
An Expanded View of Complex Traits: From Polygenic to Omnigenic [J].
Boyle, Evan A. ;
Li, Yang I. ;
Pritchard, Jonathan K. .
CELL, 2017, 169 (07) :1177-1186