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Research: Genetic effects on chromatin accessibility uncover mechanisms of liver gene regulation and quantitative traits
- Kevin W. Currin,
- Hannah J. Perrin,
- Gautam K. Pandey,
- Abdalla A. Alkhawaja,
- Swarooparani Vadlamudi,
- Annie E. Musser,
- Amy S. Etheridge,
- K. Alaine Broadaway,
- Jonathan D. Rosen,
- Arushi Varshney,
- Amarjit S. Chaudhry,
- Paul J. Gallins,
- Fred A. Wright,
- Yi-hui Zhou,
- Stephen C.J. Parker,
- Laura M. Raffield,
- Erin G. Schuetz,
- Federico Innocenti,
- and Karen L. Mohlke
Genome Res. July 2025 35: 1485-1502; Published in Advance May 20, 2025, doi:10.1101/gr.279741.124
...elements that underlie genetic effects on gene expression and metabolic traits. However, caQTL discovery has been limited by small sample sizes. Here, we map caQTLs in liver tissue from 138 human donors and identify caQTLs for 35,361 regulatory elements, including population-specific caQTLs driven...
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Method: Genetics-driven risk predictions leveraging the Mendelian randomization framework
- Daniel Sens,
- Liubov Shilova,
- Ludwig Gräf,
- Maria Grebenshchikova,
- Bjoern M. Eskofier,
- and Francesco Paolo Casale
Genome Res. September 2024 34: 1276-1285; Published in Advance September 27, 2024, doi:10.1101/gr.279252.124
.... 2010. Obesity genes and insulin resistance. Curr Opin Endocrinol Diabetes Obes 17: 472–477. doi:10.1097/MED.0b013e32833c5c48 ↵Burgess S, Thompson SG. 2015. Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol 181: 251–260. doi:10...
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Research: Mapping multitissue regulatory variants reveals a liver-centric coexpression network associated with duck egg-laying performance
- Yang Xi,
- Jingjing Qi,
- Zhao Yang,
- Yutian Zeng,
- Huicong Zhang,
- Qiuyu Tao,
- Mengru Xu,
- Anqi Huang,
- Shenqiang Hu,
- Chunchun Han,
- Lili Bai,
- Jiwei Hu,
- Jiwen Wang,
- Liang Li,
- Lingzhao Fang,
- and Hehe Liu
Genome Res. October 2025 35: 2211-2225; Published in Advance September 10, 2025, doi:10.1101/gr.280345.124
...-specific counterparts (Supplemental Fig. S3C). Subsequently, we identified 205, 756, 509, and 773 genes that had all three types of molQTL in the liver, ovary, shell gland, and spleen, respectively (Supplemental Fig. S4). To explore whether different molecular phenotypes had shared genetic architecture, we performed...
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Method: Analysis of coding gene expression from small RNA sequencing
- Aygun Azadova,
- Anthonia Ekperuoh,
- Greg N. Brooke,
- and Antonio Marco
Genome Res. March 2026 36: 611-618; Published in Advance February 10, 2026, doi:10.1101/gr.281364.125
...that in the cerebellum. Likewise, the kidney is enriched in lysine degradation, which predominantly occurs in the liver and kidney (Vaz and Wanders 2002), and the heart is enriched in hypertrophic cardiomyopathy associated genes (Sorajja et al. 2000).View this table: In this window In a new window Table 2. CC and KEGG...
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Research: Sex differences in human adipose tissue gene expression and genetic regulation involve adipogenesis
- Warren D. Anderson,
- Joon Yuhl Soh,
- Sarah E. Innis,
- Alexis Dimanche,
- Lijiang Ma,
- Carl D. Langefeld,
- Mary E. Comeau,
- Swapan K. Das,
- Eric E. Schadt,
- Johan L.M. Björkegren,
- and Mete Civelek
Genome Res. October 2020 30: 1379-1392; Published in Advance September 23, 2020, doi:10.1101/gr.264614.120
...from geographically and ethnically diverse human cohorts. The second aim was to test whether there are sex differences in the genetic architecture of gene expression in human subcutaneous adipose tissue. We specifically addressed mechanistic underpinnings of our findings throughout our analyses (Fig. 1...
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Method: Gene duplication is associated with gene diversification and potential neofunctionalization in lung cancer evolution
- Paul Ashford,
- Alexander M. Frankell,
- Zofia Piszka,
- Camilla S.M. Pang,
- Mahnaz Abbasian,
- Maise Al Bakir,
- Mariam Jamal-Hanjani,
- Nicholas McGranahan,
- Charles Swanton,
- and Christine A. Orengo
Genome Res. March 2026 36: 561-577; Published in Advance February 19, 2026, doi:10.1101/gr.278663.123
...aberrations in cell-cycle control. In non-small-cell lung cancer (NSCLC), instability occurs early in tumor growth, resulting in pronounced intratumor heterogeneity, including changes in gene copy number, and whole- doubling (WGD) in ∼75% of tumors. Gene duplication, genetic drift, and selection mediate...
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Research: Convergent relaxation of molecular constraint in herbivores reveals the changing role of liver and kidney functions across mammalian diets
- Matthew D. Pollard,
- Wynn K. Meyer,
- and Emily E. Puckett
Genome Res. December 2024 34: 2176-2189; Published in Advance November 22, 2024, doi:10.1101/gr.278930.124
...and insulin resistance increase the expression of ECM remodeling genes and encourage collagen deposition, leading to fibrosis in tissues such as skeletal muscle, liver, and adipose tissue (Choi et al. 2015; Pincu et al. 2015; Williams et al. 2015). High-fat diets and healthy glucose metabolism that resemble...
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Review: A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest
- Andrew D. Bates,
- Dawid Grzela,
- Maciej Studzian,
- Louise Brennan,
- Moli Williams,
- Conor Fawcett,
- Beth Hammond,
- Manreen Grewal,
- Marcin Ratajewski,
- Lukasz Pulaski,
- and Urszula L. McClurg
Genome Res. March 2026 36: 433-459; Published in Advance February 17, 2026, doi:10.1101/gr.281154.125
...regulatory events occur at TF binding sites some distance from the TSS, and predicting these is crucial in computational genetics. TF binding operates within a topologically associating domain typically upstream of the TSS but sometimes within the gene. However, predicting the boundaries of this domain...
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Method: Aggregation of recount3 RNA-seq data improves inference of consensus and tissue-specific gene coexpression networks
- Prashanthi Ravichandran,
- Princy Parsana,
- Rebecca Keener,
- Kasper D. Hansen,
- and Alexis Battle
Genome Res. September 2025 35: 2087-2103; Published in Advance July 17, 2025, doi:10.1101/gr.280808.125
...-specific networks (adipose, blood, CNS, liver, lung, and skin) (Methods). Details of the SNAP PPI terms that were mapped to specific tissue-contexts can be found in Supplemental Table S5. Data aggregation and increased sample size in the network significantly increased the estimated odds ratio of tissue...
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Research: A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress
- Taylor Anglen,
- Irene M. Kaplow,
- Baekgyu Choi,
- Enya Dewars,
- Robin M. Perelli,
- Kevin T. Hagy,
- Duc Tran,
- Megan E. Ramaker,
- Svati H. Shah,
- Inkyung Jung,
- Andrew P. Landstrom,
- Ravi Karra,
- Yarui Diao,
- and Charles A. Gersbach
Genome Res. November 2025 35: 2418-2432; Published in Advance October 22, 2025, doi:10.1101/gr.280825.125
...of this regulatory element on cell function and the cellular stress response. Lastly, we identify genetic variants within this enhancer that are associated with cardiac disease. These findings support a novel mechanism of myosin gene regulation and implicate myosin expression in regulating the CM response to stress...
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