Research

We are a statistical genetics laboratory interested the relationship between genes and complex disease. We have a particular focus on the use of genetically diverse experimental model organism populations, but also, where suitable intersections arise, develop and apply methods and to refine genetic inference in human populations. Specific foci include: simultaneous modeling and estimation of multiple heritable components of a complex phenotype (eg, additive, dominance, parent-of-origin, epistasis, sex-specific effects); characterizing model uncertainty in multiple quantitative trait loci (QTL) genome-wide association; modeling genetic effects on phenotypic variability; modeling gene by treatment effects (GxT), including GxE; the design of mouse resource populations for medical research; and general statistical methods for analyzing data from Multiparental genetic reference populations (MPPs). In particular, my laboratory has made advances in the design and analysis of experiments on the mouse Collaborative Cross (CC), the Heterogeneous Stock (HS) mice and rats, the mouse Diversity Outbred (DO) population, among others.

More info to come. In the meantime, see summary at unc-news and below.

Selected publications

A selection of the lab’s papers categorized by type/orientation. Selected from more than 69 publications.

Key: * equal contribution; Valdar Lab member.

Methodological papers on analysis and design of experimental populations.

Papers primarily proposing new types of model organism populations, new methods to statistically model them, or computational tools for their analysis.

  • Keele GR, Crouse WL, Kelada SNP, Valdar W (2018+) Determinants of QTL mapping power in the realized Collaborative Cross (submitted) bioRxiv 459966; doi: https://doi.org/10.1101/459966
  • Corty RW, Valdar W (2018) Mean-variance QTL mapping on a background of variance heterogeneity. G3: Genes, Genomes, Genetics (in press) PMID:30389794 bioRxiv https://doi.org/10.1101/276980
  • Corty RW, Valdar W (2018) vqtl: An R package for mean-variance QTL mapping. G3: Genes, Genomes, Genetics (in press) PMID: 30389795 bioRxiv https://doi.org/10.1101/149377
  • Oreper DG, Cai Y, Tarantino LM, Pardo-Manual de Villena F, Valdar W (2017) Inbred Strain Variant Database (ISVdb): A repository for probabilistically informed sequence differences among the Collaborative Cross strains and their founders. G3: Genes, Genomes, Genetics 7(6):1623-1630 PMID:28592645 PMCID:PMC5473744
  • Xie Y, Liu Y, Valdar W (2016) Joint estimation of multiple dependent Gaussian graphical models with applications to mouse genomics. Biometrika 103(3):493-511 PMID:29038606 PMCID:PMC5640885 doi:10.1093/biomet/asw035
  • Zhang Z, Wang W, Valdar W (2014) Bayesian modeling of haplotype effects in multiparent populations. Genetics 198:139-156 PMID:25236455 PMCID:PMC4174926
  • Crowley JJ*, Kim Y*, Lenarcic AB*, Quackenbush CR, Barrick C, Adkins DE, Shaw GS, Miller DR, Pardo Manuel de Villena F, Sullivan PF, Valdar W (2014) Genetics of adverse reactions to haloperidol in a mouse diallel: A drug-placebo experiment and Bayesian causal analysis. Genetics 196(1):321-47 PMID:24240528 PMCID:PMC3872195
  • Lenarcic AB, Svenson KL, Churchill GA, Valdar W (2012) A general Bayesian approach to analyzing diallel crosses of inbred strains. Genetics 190(2):413-435. PMID:22345610 PMCID:PMC3276624
  • Svenson KL, Gatti DM, Valdar W, Welsh CE, Cheng R, Chesler EJ, Palmer AA, McMillan L, Churchill GA (2012) The Mouse Diversity Outbred Population. Genetics 190(2):437-447. PMID:22345611 PMCID:PMC3276626
  • Ronnegard L, Valdar W (2011) Detecting major genetic loci controlling phenotypic variability in experimental crosses. Genetics 188:435-447. PMID:21467569 PMCID:PMC3122324
  • Valdar W, Holmes CC, Mott R, Flint J (2009) Mapping in structured populations by resample model averaging. Genetics 182(4):1263-77. PMID:19474203 PMCID:PMC2728864
  • Valdar W, Mott R, Flint J (2006) Simulating the collaborative cross: power of QTL detection and mapping resolution in large sets of recombinant inbred strains of mice. Genetics 172(3):1783-97. PMID:16361245 PMCID:PMC1456308
  • Valdar WSJ , Mott R, Flint J (2003) QTL fine-mapping with recombinant-inbred heterogeneous stocks and in-vitro heterogeneous stocks. Mammalian Genome 14(12):830-838. PMID:14724734

Analysis-heavy model organism experiments.

Papers describing studies on model organism experiments with a heavy statistical/computational modeling component. These usually include some aspect of bespoke statistical modeling that build upon and sometimes advance existing modeling approaches.

  • Corty RW, Kumar V, Tarantino LM, Takahashi JS, Valdar W (2018) Mean-variance QTL mapping identifies novel QTL for circadian activity and exploratory behavior in mice. G3: Genes, Genomes, Genetics (in press) PMID:30389793 bioRxiv https://doi.org/10.1101/276972
  • Oreper D, Schoenrock S, McMullan R, Ervin R, Farrington J, Miller D, Pardo-Manuel de Villena F, Valdar W*, Tarantino LM* (2018) Reciprocal F1 hybrids of two inbred mouse strains reveal parent-of-origin and perinatal diet effects on behavior and expression. G3: Genes, Genomes, Genetics 8(11):3447-3468 PMID:30171036
  • Keele GR, Prokop JW, He H, Holl K, Littrell J, Deal A, Francic S, Cui L, Gatti DM, Broman KW, Tschannen M, Tsaih S, Zagloul M, Kim Y, Baur B, Fox J, Robinson M, Levy S, Flister M, Mott R, Valdar W*, Solberg Woods LC* (2018) Genetic fine-mapping and identification of candidate genes and variants for adiposity traits in outbred rats. Obesity 26(1):213-222 PMID:29193816 PMCID:PMC5740008
  • Maurizio PL, Ferris MT, Keele GR, Miller DR, Shaw GD, Whitmore AC, West A, Morrison CR, Noll KE, Plante KS, Cockrell AS, Threadgill DW, Pardo-Manuel de Villena F, Baric RS, Heise MT, Valdar W (2018) Bayesian diallel analysis reveals Mx1-dependent and Mx1-independent effects on response to influenza A virus in mice. G3: Genes, Genomes, Genetics 8(2):427-445 PMID:29187420
  • Mosedale M*, Kim Y*, Brock WJ, Roth SE, Wiltshire T, Eaddy JS, Keele GR, Corty RW, Xie Y, Valdar W*, Watkins PB* (2017) Candidate Risk Factors and Mechanisms for Tolvaptan-Induced Liver Injury Are Identified Using a Collaborative Cross Approach. Toxicological Sciences 156(2):438-454 PMID:28115652
  • Phillippi J*, Xie Y*, Miller DR, Bell TA, Zhang Z, Lenarcic AB, Aylor DL, Krovi SH, Threadgill DW, Pardo-Manuel de Villena F, Wang W, Valdar W*, Frelinger JA* (2014) Using the Collaborative Cross to probe the immune system. Genes and Immunity 15(1):38-46 PMID:24195963 PMCID:PMC4004367
  • Calaway J, Lenarcic AB, Didion JP, Wang JR, Searle JB, McMillan L, Valdar W, Pardo-Manuel de Villena F (2013) Genetic architecture of skewed X inactivation in the laboratory mouse. PLoS Genetics 9(10):e1003853 PMID:24098153 PMCID:PMC3789830
  • Solberg Woods LC, Holl KL, Oreper D, Xie Y, Tsaih S-W, Valdar W (2012) Fine-mapping diabetes-related traits, including insulin resistance, in heterogeneous stock rats. Physiological Genomics 44(21):1013-26 PMID:22947656 PMCID:PMC3524769
  • Aylor DL, Valdar W, Foulds-Mathes W, Buus RJ, Verdugo RA, Baric RS, Ferris MT, Frelinger JA, Heise M, Frieman MB, Gralinski LE, Bell TA, Didion JP, Hua K, Nehrenberg DL, Powell CL, Steigerwalt J, Xie Y, Kelada SNP, Collins FS, Yang IV, Schwartz DA, Branstetter LA, Chesler EJ, Miller DR, Spence J, Liu EY, McMillan L, Sarkar A, Wang J, Wang W, Zhang Q, Broman KW, Korstanje R, Durrant C, Mott R, Iraqi FA, Pomp D, Threadgill D, Pardo-Manuel de Villena F, Churchill GA (2011) Genetic analysis of complex traits in the emerging Collaborative Cross. Genome Research 21(8):1213-1222. PMID:21406540 PMCID:PMC3149489
  • Johnsen AK*, Valdar W*, Golden L, Ortiz-Lopez A, Hitzemann R, Flint J, Mathis D, Benoist C (2011) Genetics of arthritis severity: a genome-wide and species-wide dissection in HS mice. Arthritis & Rheumatism 63(9):2630-2640. PMID:21560115 PMCID:PMC3371645
  • Solberg Woods L, Holl K, Tschannen M, Valdar W (2010) Fine-mapping a locus for glucose tolerance using heterogeneous stock rats. Physiological Genomics 41(1):102-8. PMID:20068026 PMCID:PMC2841497
  • Kover PX, Valdar W, Trakalo J, Scarcelli N, Ehrenreich IM, Purugganan MD, Durrant C, Mott R (2009) A Multiparent Advanced Generation Inter-Cross to fine-map quantitative traits in Arabidopsis thaliana. PLoS Genetics 5(7):e1000551 PMID:19593375 PMCID:PMC2700969
  • Valdar W, Solberg LC, Gaugier D, Cookson WO, Rawlins JNP, Mott R, Flint J (2006) Genetic and environmental effects on complex traits in mice. Genetics 174(2):959-84. PMID:16888333 PMCID:PMC1602068
  • Valdar W, Solberg LC, Gaugier D, Burnett S, Klenerman P, Cookson WO, Taylor M, Rawlins span class=”pubjournal”P, Mott R, Flint J (2006) Genome-wide genetic association of complex traits in outbred mice. Nature Genetics 38(8):879-87. PMID:16832355

Other statistical methodology, including related to human studies

  • Roach J, Valdar W (2018) Permutation tests of non-exchangeable null models. arXiv preprint arXiv:1808.10483
  • Sabourin J, Valdar W, Nobel AB (2015) A permutation approach for selecting the penalty parameter in penalized model selection. Biometrics 71(4):1185-94. PMID:26243050 PMCID:PMC4314429
  • Sabourin J, Nobel AB, Valdar W (2015) Fine-mapping additive and dominant SNP effects using group-LASSO and Fractional Resample Model Averaging Genetic Epidemiology 39(2):77-88 PMID:25417853 PMCID:PMC4314429
  • Valdar W*, Sabourin J*, Nobel A, Holmes C (2012) Reprioritizing genetic associations in hit regions using LASSO-based resample model averaging. Genetic Epidemiology 36(5):451-462 PMID:22549815 PMCID:PMC3470705

Reviews

  • Ronnegard L, Valdar W (2012) Recent developments in statistical methods for detecting genetic loci affecting phenotypic variability. BMC Genetics 13(1):63 PMID:22827487 PMCID:PMC3493319
  • Willis-Owen SAG, Valdar W (2009) Deciphering gene-environment interactions through mouse models of allergic asthma. Journal of Allergy and Clinical Immunology 123(1):14-23. PMID:18926561
  • Flint J, Valdar W, Shifman S, Mott R (2005) Experimental strategies for mapping and cloning quantitative trait genes in rodents. Nature Reviews Genetics 6(4):271-286. PMID:15803197