Deep learning and genome-wide association meta-analyses of bone marrow adiposity in the UK Biobank

被引:0
|
作者
Xu, Wei [1 ,2 ]
Mesa-Eguiagaray, Ines [1 ]
Morris, David M. [2 ,3 ]
Wang, Chengjia [3 ,4 ]
Gray, Calum D. [3 ]
Sjostrom, Samuel [2 ]
Papanastasiou, Giorgos [3 ,5 ]
Badr, Sammy [6 ]
Paccou, Julien [6 ]
Li, Xue [7 ]
Timmers, Paul R. H. J. [8 ]
Timofeeva, Maria [8 ,9 ]
Farrington, Susan M. [10 ,11 ]
Dunlop, Malcolm G. [10 ,11 ]
Semple, Scott I. [2 ,3 ]
Macgillivray, Tom [12 ]
Theodoratou, Evropi [1 ,13 ]
Cawthorn, William P. [2 ]
机构
[1] Univ Edinburgh, Usher Inst, Ctr Global Hlth & Mol Epidemiol, Edinburgh, Scotland
[2] Univ Edinburgh, Queens Med Res Inst, Univ BHF Ctr Cardiovasc Sci, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, Scotland
[3] Univ Edinburgh, Queens Med Res Inst, Edinburgh Imaging, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, Scotland
[4] Heriot Watt Univ, Sch Math & Comp Sci, Edinburgh, Scotland
[5] Athena Res Ctr, Archimedes Unit, Maroussi 15125, Greece
[6] Univ Lille, Dept Rheumatol, Marrow Adipos & Bone Lab MABlab ULR 4490, CHU Lille, Lille, France
[7] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Sch Publ Hlth,Dept Big Data Hlth Sci, Hangzhou, Peoples R China
[8] Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Scotland
[9] Univ Southern Denmark, Danish Inst Adv Study DIAS Epidemiol Biostat & Bio, Dept Publ Hlth, Odense, Denmark
[10] Univ Edinburgh, Inst Genet & Canc, Canc Res UK Edinburgh Ctr, MRC, Edinburgh, Scotland
[11] Univ Edinburgh, Inst Genet & Canc, Colon Canc Genet Grp, Edinburgh, Scotland
[12] Univ Edinburgh, Queens Med Res Inst, Ctr Clin Brain Sci, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, Scotland
[13] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh Canc Res Ctr, Edinburgh, Scotland
基金
英国医学研究理事会;
关键词
CALORIC RESTRICTION; TISSUE; CELL; DIFFERENTIATION; SPECTROSCOPY; REGRESSION; ESTROGEN; YOUNGER; LEPTIN; MRI;
D O I
10.1038/s41467-024-55422-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Bone marrow adipose tissue is a distinct adipose subtype comprising more than 10% of fat mass in healthy humans. However, the functions and pathophysiological correlates of this tissue are unclear, and its genetic determinants remain unknown. Here, we use deep learning to measure bone marrow adiposity in the femoral head, total hip, femoral diaphysis, and spine from MRI scans of approximately 47,000 UK Biobank participants, including over 41,000 white and over 6300 non-white participants. We then establish the heritability and genome-wide significant associations for bone marrow adiposity at each site. Our meta-GWAS in the white population finds 67, 147, 134, and 174 independent significant single nucleotide polymorphisms, which map to 54, 90, 43, and 100 genes for the femoral head, total hip, femoral diaphysis, and spine, respectively. Transcriptome-wide association studies, colocalization analyses, and sex-stratified meta-GWASes in the white participants further resolve functional and sex-specific genes associated with bone marrow adiposity at each site. Finally, we perform a multi-ancestry meta-GWAS to identify genes associated with bone marrow adiposity across the different bone regions and across ancestry groups. Our findings provide insights into BMAT formation and function and provide a basis to study the impact of BMAT on human health and disease.
引用
收藏
页数:19
相关论文
共 50 条
  • [31] Cross-ancestry genome-wide association meta-analyses of hippocampal and subfield volumes
    Nana Liu
    Longjiang Zhang
    Tian Tian
    Jingliang Cheng
    Bing Zhang
    Shijun Qiu
    Zuojun Geng
    Guangbin Cui
    Quan Zhang
    Weihua Liao
    Yongqiang Yu
    Hui Zhang
    Bo Gao
    Xiaojun Xu
    Tong Han
    Zhenwei Yao
    Wen Qin
    Feng Liu
    Meng Liang
    Qiang Xu
    Jilian Fu
    Jiayuan Xu
    Wenzhen Zhu
    Peng Zhang
    Wei Li
    Dapeng Shi
    Caihong Wang
    Su Lui
    Zhihan Yan
    Feng Chen
    Jiance Li
    Jing Zhang
    Dawei Wang
    Wen Shen
    Yanwei Miao
    Junfang Xian
    Jia-Hong Gao
    Xiaochu Zhang
    Mulin Jun Li
    Kai Xu
    Xi-Nian Zuo
    Meiyun Wang
    Zhaoxiang Ye
    Chunshui Yu
    Nature Genetics, 2023, 55 : 1126 - 1137
  • [32] Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics
    Agrawal, Arpana
    Edenberg, Howard J.
    Gelernter, Joel
    JOURNAL OF STUDIES ON ALCOHOL AND DRUGS, 2016, 77 (05) : 676 - 680
  • [33] Methods For Meta-Analyses Of Genome-Wide Association Studies: Critical Assessment Of Empirical Evidence
    Minelli, Cosetta
    Gogele, Martin
    Thakkinstian, Ammarin
    Yurkiewich, Alex
    Pattaro, Cristian
    Pramstaller, Peter P.
    Little, Julian
    Attia, John
    Thompson, John R.
    GENETIC EPIDEMIOLOGY, 2012, 36 (02) : 147 - 147
  • [34] On Genome-wide Association Studies and their Meta-analyses - Lessons Learned from Osteoporosis Studies
    Liu, Yongjun
    Zhang, Lei
    Pei, Yufang
    Papasian, Christopher
    Deng, Hong-Wen
    JOURNAL OF BONE AND MINERAL RESEARCH, 2013, 28
  • [35] Cross-ancestry genome-wide association meta-analyses of hippocampal and subfield volumes
    Liu, Nana
    Zhang, Longjiang
    Tian, Tian
    Cheng, Jingliang
    Zhang, Bing
    Qiu, Shijun
    Geng, Zuojun
    Cui, Guangbin
    Zhang, Quan
    Liao, Weihua
    Yu, Yongqiang
    Zhang, Hui
    Gao, Bo
    Xu, Xiaojun
    Han, Tong
    Yao, Zhenwei
    Qin, Wen
    Liu, Feng
    Liang, Meng
    Xu, Qiang
    Fu, Jilian
    Xu, Jiayuan
    Zhu, Wenzhen
    Zhang, Peng
    Li, Wei
    Shi, Dapeng
    Wang, Caihong
    Lui, Su
    Yan, Zhihan
    Chen, Feng
    Li, Jiance
    Zhang, Jing
    Wang, Dawei
    Shen, Wen
    Miao, Yanwei
    Xian, Junfang
    Gao, Jia-Hong
    Zhang, Xiaochu
    Li, Mulin Jun
    Xu, Kai
    Zuo, Xi-Nian
    Wang, Meiyun
    Ye, Zhaoxiang
    Yu, Chunshui
    CHIMGEN Consortium
    NATURE GENETICS, 2023, 55 (07) : 1126 - +
  • [36] On Genome-Wide Association Studies and Their Meta-Analyses: Lessons Learned From Osteoporosis Studies
    Liu, Yong-Jun
    Zhang, Lei
    Pei, Yufang
    Papasian, Christopher J.
    Deng, Hong-Wen
    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2013, 98 (07): : E1278 - E1282
  • [37] GENOME-WIDE AND EXOME-CHIP ASSOCIATION META-ANALYSES OF THE HEALTH AGING INDEX
    Minster, R.
    Sanders, J.
    Lunetta, K.
    Murabito, J. M.
    Newman, A. B.
    GERONTOLOGIST, 2015, 55 : 8 - 8
  • [38] INTEGRATING GENOME-WIDE META-ANALYSES OF BINARY AND CONTINUOUS PHENOTYPES
    Walters, Raymond
    EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2017, 27 : S350 - S351
  • [39] Genome-wide association analyses identify 139 loci associated with macular thickness in the UK Biobank cohort
    Gao, X. Raymond
    Huang, Hua
    Kim, Heejin
    HUMAN MOLECULAR GENETICS, 2019, 28 (07) : 1162 - 1172
  • [40] Genome-wide association study of multisite chronic pain in UK Biobank
    Johnston, Keira J. A.
    Adams, Mark J.
    Nicholl, Barbara I.
    Ward, Joey
    Strawbridge, Rona J.
    Ferguson, Amy
    McIntosh, Andrew M.
    Bailey, Mark E. S.
    Smith, Daniel J.
    PLOS GENETICS, 2019, 15 (06):