Myostatin dysfunction is associated with reduction in overload induced hypertrophy of soleus muscle in mice

Acknowledgements This project was also supported by Marie Curie International Reintegration Grant 249156 (A. Lionikas) and the grants VP1-3.1-SMM-01-V-02-003 (A. Kilikevicius) and MIP-067/2012 (T. Venckunas) from the Research Council of Lithuania as well as the grant from the Ministry of Higher Education of Saudi Arabia (Y. Alhind). We wish also to thank Mrs Indre Libnickiene for her excellent technical assistance provided during the project.Peer reviewedPostprin

Baseline Muscle Mass Is a Poor Predictor of Functional Overload-Induced Gain in the Mouse Model

This research was funded by the European Social Fund under the Global Grant measure. Grant VP1-3.1-ŠMM-07-K-02-057 was awarded to AL.Peer reviewedPublisher PD

QTL analyses of temporal and intensity components of home-cage activity in KJR and C57BL/6J strains

Peer reviewedPublisher PD

Resolving candidate genes of mouse skeletal muscle QTL via RNA-Seq and expression network analyses

Peer reviewedPublisher PD

Replication and discovery of musculoskeletal QTLs in LG/J and SM/J advanced intercross lines

AR056280 awarded to DAB and AL. AIHC supported by IMS and Elphinstone Scholarship from the University of Aberdeen. GRV supported by Medical Research Scotland (Vac-929-2016).Peer reviewedPublisher PD

Validation of positional candidates Rps6ka6 and Pou3f4 for a locus associated with skeletal muscle mass variability

Open Acess via the OUP Agreement Acknowledgments Authors are grateful for Mr James Archibald for assistance with histological analysis of muscle samples and for the Microscopy and Histology Core Facility at the University of Aberdeen for the help with imaging. Funding A.L. was supported by awards AR052879 and AR056280 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, award 249156 from the FP7-PEOPLE-2009-RG programme, award CGA/18/05 from the Chief Scientist Office, award 21/019 from the NHS Grampian, and award 204815/Z/16/Z from the Wellcome Trust. T.M.C. was supported by NIH R01 DC016595. P.M.B. was supported by NIH R01 DC016595, NIH F31 DC019824, and TL1TR001431. Research reported in this article was supported by the National Center for Advancing Translational Sciences under award number TL1TR001431. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Peer reviewe

Analysis of independent cohorts of outbred CFW mice reveals novel loci for behavioral and physiological traits and identifies factors determining reproducibility

Combining samples for genetic association is standard practice in human genetic analysis of complex traits, but is rarely undertaken in rodent genetics. Here, using 23 phenotypes and genotypes from two independent laboratories, we obtained a sample size of 3,076 commercially available outbred mice and identified 70 loci, more than double the number of loci identified in the component studies. Fine-mapping in the combined sample reduced the number of likely causal variants, with a median reduction in set size of 51%, and indicated novel gene associations, including Pnpo, Ttll6 and GM11545 with bone mineral density, and Psmb9 with weight. However replication at a nominal threshold of 0.05 between the two component studies was low, with less than a third of loci identified in one study replicated in the second. In addition to overestimates in the effect size in the discovery sample (Winner's Curse), we also found that heterogeneity between studies explained the poor replication, but the contribution of these two factors varied among traits. Leveraging these observations we integrated information about replication rates, study-specific heterogeneity, and Winner's Curse corrected estimates of power to assign variants to one of four confidence levels. Our approach addresses concerns about reproducibility, and demonstrates how to obtain robust results from mapping complex traits in any genome-wide association study

Fine mapping of genes determining extrafusal fiber properties in murine soleus muscle

Peer reviewedPostprin

Analysis of independent cohorts of outbred CFW mice reveals novel loci for behavioral and physiological traits and identifies factors determining reproducibility

Combining samples for genetic association is standard practice in human genetic analysis of complex traits, but is rarely undertaken in rodent genetics. Here, using 23 phenotypes and genotypes from two independent laboratories, we obtained a sample size of 3076 commercially available outbred mice and identified 70 loci, more than double the number of loci identified in the component studies. Fine-mapping in the combined sample reduced the number of likely causal variants, with a median reduction in set size of 51%, and indicated novel gene associations, including Pnpo, Ttll6, and GM11545 with bone mineral density, and Psmb9 with weight. However, replication at a nominal threshold of 0.05 between the two component studies was low, with less than one-third of loci identified in one study replicated in the second. In addition to overestimates in the effect size in the discovery sample (Winner’s Curse), we also found that heterogeneity between studies explained the poor replication, but the contribution of these two factors varied among traits. Leveraging these observations, we integrated information about replication rates, study-specific heterogeneity, and Winner’s Curse corrected estimates of power to assign variants to one of four confidence levels. Our approach addresses concerns about reproducibility and demonstrates how to obtain robust results from mapping complex traits in any genome-wide association study