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Method: ML-MAGES enables multivariate genetic association analyses with genes and effect size shrinkage
- Xiran Liu,
- Lorin Crawford,
- and Sohini Ramachandran
Genome Res. December 2025 35: 2691-2700; Published in Advance November 19, 2025, doi:10.1101/gr.280440.125
.... S6), suggesting that our model is not sensitive to the specific chromosomes used for generating training data.Application to real dataApplication to quantitative traits: HDL and LDL cholesterolTo get a comprehensive understanding of how different shrinkage methods affect gene-level analysis, we...
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Research: Epigenetic drift score captures directional methylation variability and links aging to transcriptional, metabolic, and genetic alterations
- Xiu Fan,
- Qili Qian,
- Wenran Li,
- Tianzi Liu,
- Changqing Zeng,
- Peilin Jia,
- Huandong Lin,
- Xin Gao,
- Li Jin,
- Mingfeng Xia,
- Sijia Wang,
- and Fan Liu
Genome Res. October 2025 35: 2173-2188; Published in Advance August 1, 2025, doi:10.1101/gr.280155.124
...sequencing (e.g., WGBS) to resolve single-molecule differences. Although we also calculated individual-level entropy from array data, our primary objective was to model changes in methylation variance with age across the population, enabling the identification of drift-CpGs that reflect systemic...
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LETTER: Using Advanced Intercross Lines for High-Resolution Mapping of HDL Cholesterol Quantitative Trait Loci
- Xiaosong Wang,
- Isabelle Le Roy,
- Edwige Nicodeme,
- Renhua Li,
- Richard Wagner,
- Christina Petros,
- Gary A. Churchill,
- Stephen Harris,
- Ariel Darvasi,
- Jorge Kirilovsky,
- Pierre L. Roubertoux,
- and Beverly Paigen
Genome Res. July 2003 13: 1654-1664; Published in Advance June 12, 2003, doi:10.1101/gr.1185803
...backcross progeny fed either chow or an atherogenic diet to detect QTLs that regulate high-density lipoprotein cholesterol (HDL)concentrations, and in (C57BL/6J × NZB/BlNJ)F 11 AIL progeny to confirm and narrow those QTLs. QTLs for HDL concentrations were found on chromosomes 1, 5, and 16. AIL not only...
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LETTER: Microarray Expression Profiling Identifies Genes with Altered Expression in HDL-Deficient Mice
- Matthew J. Callow,
- Sandrine Dudoit,
- Elaine L. Gong,
- Terence P. Speed,
- and Edward M. Rubin
Genome Res. December 1, 2000 10: 2022-2029; doi:10.1101/gr.147200
...Based on the assumption that severe alterations in the expression of genes known to be involved in high-density lipoprotein (HDL) metabolism may affect the expression of other genes, we screened an array of &gt;5000 mouse expressed sequence tags for altered gene expression in the livers of two lines...
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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
...accessibility, gene expression, and a GWAS trait. At an example near TGFB1, a caQTL for caPeak156441 is colocalized with an eQTL for TGFB1 and GWAS signals for levels of gamma-glutamyltransferase (GGT) (Fig. 4C), high-density lipoprotein (HDL) cholesterol, and coronary artery disease. Variant rs56254331 within...
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PERSPECTIVE: Genomics of the future: Identification of quantitative trait loci in the mouse
- Lorraine Flaherty,
- Bruce Herron,
- and Derek Symula
Genome Res. December 2005 15: 1741-1745; doi:10.1101/gr.3841405
...them difficult to isolate and they often have a low penetrance. Positional cloning of these QTLs in rodents has proved to be one of the most powerful tools for the functional identification of these genes ( Georges 1997 ). The first step in this procedure is to map these loci to particular chromosomal...
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Review: Advancing genomic technologies and clinical awareness accelerates discovery of disease-associated tandem repeat sequences
- Terence Gall-Duncan,
- Nozomu Sato,
- Ryan K.C. Yuen,
- and Christopher E. Pearson
Genome Res. January 2022 32: 1-27; Published in Advance December 29, 2021, doi:10.1101/gr.269530.120
...of spinocerebellar ataxia type 7 (SCA7) (Lindblad et al. 1996), SCA12 (Holmes et al. 1999), Huntington disease-like 2 (HDL2) (Holmes et al. 2001; Margolis et al. 2001) and CTG18.1 (Breschel et al. 1997); DIRECT led to the identification of the ATXN2 mutation (Sanpei et al. 1996) and RAPID to the SCA8 repeat...
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Review: Contrasting genetic architectures in different mouse reference populations used for studying complex traits
- David A. Buchner and
- Joseph H. Nadeau
Genome Res. June 2015 25: 775-791; Published in Advance May 7, 2015, doi:10.1101/gr.187450.114
...specialized resources have been developed to study complex traits in many model organisms. In the mouse, remarkably different pictures of genetic architectures are emerging. Chromosome Substitution Strains (CSSs) reveal many QTLs, large phenotypic effects, pervasive epistasis, and readily identified genetic...
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Resource: A high-resolution association mapping panel for the dissection of complex traits in mice
- Brian J. Bennett,
- Charles R. Farber,
- Luz Orozco,
- Hyun Min Kang,
- Anatole Ghazalpour,
- Nathan Siemers,
- Michael Neubauer,
- Isaac Neuhaus,
- Roumyana Yordanova,
- Bo Guan,
- Amy Truong,
- Wen-pin Yang,
- Aiqing He,
- Paul Kayne,
- Peter Gargalovic,
- Todd Kirchgessner,
- Calvin Pan,
- Lawrence W. Castellani,
- Emrah Kostem,
- Nicholas Furlotte,
- Thomas A. Drake,
- Eleazar Eskin,
- and Aldons J. Lusis
Genome Res. February 2010 20: 281-290; Published in Advance January 6, 2010, doi:10.1101/gr.099234.109
...in the identification of 2691 probes with local (commonly called cisacting) expression quantitative trait loci (eQTL) and 3174 probes with at least one distal (trans-acting) eQTL at a P-value of #4.1 3 10#2;6. Figure 2A shows a plot of the location of each of the genes on the array (y-axis) and the corresponding...
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Research: Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits
- Peter Orchard,
- Nandini Manickam,
- Christa Ventresca,
- Swarooparani Vadlamudi,
- Arushi Varshney,
- Vivek Rai,
- Jeremy Kaplan,
- Claudia Lalancette,
- Karen L. Mohlke,
- Katherine Gallagher,
- Charles F. Burant,
- and Stephen C.J. Parker
Genome Res. December 2021 31: 2258-2275; Published in Advance November 23, 2021, doi:10.1101/gr.268482.120
...highlighted by our data is the ITPR2 locus on Chromosome 12 (Fig. 4B). This locus contains 22 credible set SNPs, none with a particularly high posterior probability of association (PPA) in the DIAMANTE genetic fine-mapping (maximum across all credible set SNPs = 0.06). Only one SNP (rs7132434; PPA = 0...

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