Iryna Lobach, PhD
Associate Professor
Epidemiology & Biostatistics
School of Medicine

Her methodological research interests are motivated by challenges arising in the analyses of how an effect of the genetic basis varies by non-genetic measures (environment), what is traditionally referred to as gene-environment interaction (GxE) analyses. This type of analyses might provide valuable clues to the underlying pathophysiologic mechanisms of complex phenotypes.

For example, in collaboration with statisticians and biomedical researchers, Dr. Lobach developed an efficient retrospective analysis of case-control genetic studies in situations when the environmental variable is measured with error, e.g. diet or physical activity. Both in theory and in practice, this method improves efficiency of the risk parameter estimates and is capable of correcting coverage of 95% Confidence Intervals from e.g. 68% of the standard approach to the nominal 95% in a practical example of analyses of association between calcium intake and the risk of colorectal adenoma analyses.

We developed statistical methods to incorporate heterogeneity of the clinical diagnosis characterized by biomarker studies in situations when 1) multiple distinct pathophysiologic mechanisms share symptoms and hence the clinical diagnosis; and 2) substantial segments of the population are undiagnosed. We show that the genetic variant will appear to interact with the environmental variable if the genetic variant affects the pathologically defined disease state and the environmental variable is related to the proportion of cases with that disease state. We then propose a pseudo-likelihood solution and apply the methods to large genome-wide studies of Prostate Cancer and Alzheimer’s disease.

Recently, we developed case-only estimates of GxE in settings when 1) multiple disease state share the clinical diagnosis, 2) frequencies of the disease state of interest within the clinical diagnosis vary by the E or other variables, 3) both clinical diagnosis and the disease states are common. We show the application to Alzheimer's disease.

We are also conducting studies to investigate bias in the genetic effect estimates due to omitting a continuous variable. Specifically, we are interested to assess what information is needed to correct the bias if the actual values of the continuous variable are not available to the researcher. For example, many of the genetic databases offer only a brief set of non-genetic variables. We show the application to Alzheimer's disease (https://www.biorxiv.org/content/10.1101/756015v1).

We have recently studied whether a case-only study of GxE is better than a case-control study in the context when the disease state is common and when the multiple distinct disease states share a clinical diagnosis. We investigated differences in the GxE estimates in the context of Alzheimer's disease (https://www.biorxiv.org/content/10.1101/760322v1).

Dr. Lobach supports the biostatistics component of multiple biomedical studies through collaboration, consultation (CTSI biostatistics consultant) and mentoring (K-grants, mentoring in the Training in Clinical Research Program).

• Pericardial Fat Enhancement: New Computed Tomography Biomarker Influences the Relationship Between Pericardial Fat and Coronary Artery Disease.
  Journal of thoracic imaging 2020 Kallianos KG, Lorca MC, Moraes GL, Devcic Z, Lobach I, Ordovas KG
• Performance of screening MRI in high risk patients at initial versus subsequent screen.
  Clinical imaging 2020 Hayward JH, Ray KM, Price ER, Sickles EA, Conlon K, Lobach I, Joe BN, Lee AY
• Factors Predicting Metastatic Disease in 68Ga-PSMA-11 PET-Positive Osseous Lesions in Prostate Cancer.
  Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2020 Chiu LW, Lawhn-Heath C, Behr SC, Juarez R, Perez PM, Lobach I, Bucknor MD, Hope TA, Flavell RR
• A systematic review and meta-analysis examining the effects of cannabis and its derivatives in adults with malignant CNS tumors.
  Neuro-oncology practice 2020 Rodriguez-Almaraz JE, Chang S, Clarke J, Oberheim-Bush NA, Taylor J, Buerki R, Berger M, Zablotska L, Lobach I, Butowski N
• Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development.
  Neuron 2020 Lennox AL, Hoye ML, Jiang R, Johnson-Kerner BL, Suit LA, Venkataramanan S, Sheehan CJ, Alsina FC, Fregeau B, Aldinger KA, Moey C, Lobach I, Afenjar A, Babovic-Vuksanovic D, Bézieau S, Blackburn PR, …
• Case-control versus case-only estimates of gene-environment interactions with common and misclassified clinical diagnosis.
  Genetic epidemiology 2019 Lobach I, Sheng Y, Lobach S, Zablotska L, Huang CY
• Hyperpolarized in vivo pH imaging reveals grade-dependent acidification in prostate cancer.
  Oncotarget 2019 Korenchan DE, Bok R, Sriram R, Liu K, Santos RD, Qin H, Lobach I, Korn N, Wilson DM, Kurhanewicz J, Flavell RR
• A Simple Approximation to Bias in Gene-Environment Interaction Estimates When a Case Might Not Be the Case.
  Frontiers in genetics 2019 Lobach I, Kim I, Alekseyenko A, Lobach S, Zhang L
• The impact of technical parameters on ablation volume during MR-guided focused ultrasound of desmoid tumors.
  International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 2019 Bucknor MD, Beroukhim G, Rieke V, Ozhinsky E, Lobach I
• A simple approximation to bias in the genetic effect estimates when multiple disease states share a clinical diagnosis.
  Genetic epidemiology 2019 Lobach I, Kim I, Alekseyenko A, Lobach S, Zhang L
• A simple approximation to the bias of gene-environment interactions in case-control studies with silent disease.
  Genetic epidemiology 2019 Lobach I, Sampson J, Lobach S, Alekseyenko A, Piryatinska A, He T, Zhang L
• The Gambler's Fallacy in Screening Mammography.
  Journal of the American College of Radiology : JACR 2019 Callen AL, Lobach I, Mesina O, Marcus S, Joe BN, Sickles EA, Greenwood HI
• Female XX sex chromosomes increase survival and extend lifespan in aging mice.
  Aging cell 2018 Davis EJ, Lobach I, Dubal DB
• Bias in parameter estimates due to omitting gene-environment interaction terms in case-control studies.
  Genetic epidemiology 2018 Lobach I
• Microcalcifications Detected at Screening Mammography: Synthetic Mammography and Digital Breast Tomosynthesis versus Digital Mammography.
  Radiology 2018 Lai YC, Ray KM, Lee AY, Hayward JH, Freimanis RI, Lobach IV, Joe BN
• Case-control studies of gene-environment interactions. When a case might not be the case.
  PloS one 2018 Lobach I, Sampson J, Alekseyenko A, Lobach S, Zhang L
• Gene-environment interactions in case-control studies with silent disease.
  Genetic epidemiology 2018 Lobach I, Sampson J, Lobach S, Zhang L
• Rates of Amyloid Imaging Positivity in Patients With Primary Progressive Aphasia.
  JAMA neurology 2018 Santos-Santos MA, Rabinovici GD, Iaccarino L, Ayakta N, Tammewar G, Lobach I, Henry ML, Hubbard I, Mandelli ML, Spinelli E, Miller ZA, Pressman PS, O'Neil JP, Ghosh P, Lazaris A, Meyer M, Watson C, …
• Synovial Fluid Profile at the Time of Anterior Cruciate Ligament Reconstruction and Its Association With Cartilage Matrix Composition 3 Years After Surgery.
  The American journal of sports medicine 2018 Amano K, Huebner JL, Stabler TV, Tanaka M, McCulloch CE, Lobach I, Lane NE, Kraus VB, Ma CB, Li X
• CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP.
  Neurology 2017 Rojas JC, Bang J, Lobach IV, Tsai RM, Rabinovici GD, Miller BL, Boxer AL, AL-108-231 Investigators
• Effect of Background Parenchymal Enhancement on Breast MR Imaging Interpretive Performance in Community-based Practices.
  Radiology 2017 Ray KM, Kerlikowske K, Lobach IV, Hofmann MB, Greenwood HI, Arasu VA, Hylton NM, Joe BN
• Clustered Microcysts on Breast Ultrasound: What Is an Appropriate Management Recommendation?
  AJR. American journal of roentgenology 2017 Greenwood HI, Lee AY, Lobach IV, Carpentier BM, Freimanis RI, Strachowski LM
• Altered cargo proteins of human plasma endothelial cell-derived exosomes in atherosclerotic cerebrovascular disease.
  FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2017 Goetzl EJ, Schwartz JB, Mustapic M, Lobach IV, Daneman R, Abner EL, Jicha GA
• A multicenter study to define sarcopenia in patients with end-stage liver disease.
  Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2017 Carey EJ, Lai JC, Wang CW, Dasarathy S, Lobach I, Montano-Loza AJ, Dunn MA, Fitness, Life Enhancement, and Exercise in Liver Transplantation Consortium
• Tau prions from Alzheimer's disease and chronic traumatic encephalopathy patients propagate in cultured cells.
  Proceedings of the National Academy of Sciences of the United States of America 2016 Woerman AL, Aoyagi A, Patel S, Kazmi SA, Lobach I, Grinberg LT, McKee AC, Seeley WW, Olson SH, Prusiner SB
• Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by disease stage.
  Neurology 2016 Bertoux M, Sarazin M, Pasquier F, Bottlaender M, de Souza LC, Mioshi E, Hornberger M, Ranasinghe KG, Rankin KP, Lobach IV, Kramer JH, Sturm VE, Bettcher BM, Possin K, You SC, Lamarre AK, Shany-Ur T, …
• Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro.
  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2016 Heilmeier U, Hackl M, Skalicky S, Weilner S, Schroeder F, Vierlinger K, Patsch JM, Baum T, Oberbauer E, Lobach I, Burghardt AJ, Schwartz AV, Grillari J, Link TM
• Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease.
  FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2016 Goetzl EJ, Kapogiannis D, Schwartz JB, Lobach IV, Goetzl L, Abner EL, Jicha GA, Karydas AM, Boxer A, Miller BL
• Distinct Subtypes of Behavioral Variant Frontotemporal Dementia Based on Patterns of Network Degeneration.
  JAMA neurology 2016 Ranasinghe KG, Rankin KP, Pressman PS, Perry DC, Lobach IV, Seeley WW, Coppola G, Karydas AM, Grinberg LT, Shany-Ur T, Lee SE, Rabinovici GD, Rosen HJ, Gorno-Tempini ML, Boxer AL, Miller ZA, Chiong W,…
• Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma.
  The Journal of clinical investigation 2016 Daud AI, Loo K, Pauli ML, Sanchez-Rodriguez R, Sandoval PM, Taravati K, Tsai K, Nosrati A, Nardo L, Alvarado MD, Algazi AP, Pampaloni MH, Lobach IV, Hwang J, Pierce RH, Gratz IK, Krummel MF, Rosenblum…
• Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer's disease.
  FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2016 Goetzl EJ, Mustapic M, Kapogiannis D, Eitan E, Lobach IV, Goetzl L, Schwartz JB, Miller BL
• Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.
  Journal of thrombosis and thrombolysis 2016 Roswell RO, Greet B, Shah S, Bernard S, Milin A, Lobach I, Guo Y, Radford MJ, Berger JS
• Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy.
  Parkinsonism & related disorders 2016 Tsai RM, Lobach I, Bang J, Whitwell JL, Senjem ML, Jack CR, Rosen H, Miller B, Boxer AL, AL-108-231 Investigators
• Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials.
  Parkinsonism & related disorders 2016 Bang J, Lobach IV, Lang AE, Grossman M, Knopman DS, Miller BL, Schneider LS, Doody RS, Lees A, Gold M, Morimoto BH, Boxer AL, AL-108-231 Investigators
• Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy.
  Movement disorders : official journal of the Movement Disorder Society 2016 Stamelou M, Schöpe J, Wagenpfeil S, Del Ser T, Bang J, Lobach IY, Luong P, Respondek G, Oertel WH, Boxer A, Höglinger GU, AL-108-231 Investigators, Tauros Investigators, and MDS-Endorsed PSP Study …
• Adverse Trends in Ischemic Heart Disease Mortality among Young New Yorkers, Particularly Young Black Women.
  PloS one 2016 Smilowitz NR, Maduro GA, Lobach IV, Chen Y, Reynolds HR
• Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by disease stage.
  Neurology 2016 Ranasinghe KG, Rankin KP, Lobach IV, Kramer JH, Sturm VE, Bettcher BM, Possin K, Christine You S, Lamarre AK, Shany-Ur T, Stephens ML, Perry DC, Lee SE, Miller ZA, Gorno-Tempini ML, Rosen HJ, Boxer A,…
• Identifying preoperative language tracts and predicting postoperative functional recovery using HARDI q-ball fiber tractography in patients with gliomas.
  Journal of neurosurgery 2015 Caverzasi E, Hervey-Jumper SL, Jordan KM, Lobach IV, Li J, Panara V, Racine CA, Sankaranarayanan V, Amirbekian B, Papinutto N, Berger MS, Henry RG
• Association Between Thoracic Spinal Cord Gray Matter Atrophy and Disability in Multiple Sclerosis.
  JAMA neurology 2015 Schlaeger R, Papinutto N, Zhu AH, Lobach IV, Bevan CJ, Bucci M, Castellano A, Gelfand JM, Graves JS, Green AJ, Jordan KM, Keshavan A, Panara V, Stern WA, von Büdingen HC, Waubant E, Goodin DS, Cree BA…
• Gene Level Meta-Analysis of Quantitative Traits by Functional Linear Models.
  Genetics 2015 Fan R, Wang Y, Boehnke M, Chen W, Li Y, Ren H, Lobach I, Xiong M
• Comparing CSF biomarkers and brain MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease.
  Neurology. Clinical practice 2015 Forner SA, Takada LT, Bettcher BM, Lobach IV, Tartaglia MC, Torres-Chae C, Haman A, Thai J, Vitali P, Neuhaus J, Bostrom A, Miller BL, Rosen HJ, Geschwind MD
• Diabetes and ischemic heart disease death in people age 25-54: a multiple-cause-of-death analysis based on over 400 000 deaths from 1990 to 2008 in New York City.
  Clinical cardiology 2015 Quinones A, Lobach I, Maduro GA, Smilowitz NR, Reynolds HR
• White matter involvement in sporadic Creutzfeldt-Jakob disease.
  Brain : a journal of neurology 2014 Caverzasi E, Mandelli ML, DeArmond SJ, Hess CP, Vitali P, Papinutto N, Oehler A, Miller BL, Lobach IV, Bastianello S, Geschwind MD, Henry RG
• A risk score for prediction of hyperglycemia at coronary angiography.
  JACC. Cardiovascular interventions 2014 Shah B, Burdowski J, Lobach I, Gianos E, Sedlis SP
• Generalized functional linear models for gene-based case-control association studies.
  Genetic epidemiology 2014 Fan R, Wang Y, Mills JL, Carter TC, Lobach I, Wilson AF, Bailey-Wilson JE, Weeks DE, Xiong M
• Interleukin-6, age, and corpus callosum integrity.
  PloS one 2014 Bettcher BM, Watson CL, Walsh CM, Lobach IV, Neuhaus J, Miller JW, Green R, Patel N, Dutt S, Busovaca E, Rosen HJ, Yaffe K, Miller BL, Kramer JH
• Spinal cord gray matter atrophy correlates with multiple sclerosis disability.
  Annals of neurology 2014 Schlaeger R, Papinutto N, Panara V, Bevan C, Lobach IV, Bucci M, Caverzasi E, Gelfand JM, Green AJ, Jordan KM, Stern WA, von Büdingen HC, Waubant E, Zhu AH, Goodin DS, Cree BA, Hauser SL, Henry RG
• Frontal white matter tracts sustaining speech production in primary progressive aphasia.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2014 Mandelli ML, Caverzasi E, Binney RJ, Henry ML, Lobach I, Block N, Amirbekian B, Dronkers N, Miller BL, Henry RG, Gorno-Tempini ML
• Divergent CSF τ alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy.
  Journal of neurology, neurosurgery, and psychiatry 2014 Wagshal D, Sankaranarayanan S, Guss V, Hall T, Berisha F, Lobach I, Karydas A, Voltarelli L, Scherling C, Heuer H, Tartaglia MC, Miller Z, Coppola G, Ahlijanian M, Soares H, Kramer JH, Rabinovici GD, …
• Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial.
  The Lancet. Neurology 2014 Boxer AL, Lang AE, Grossman M, Knopman DS, Miller BL, Schneider LS, Doody RS, Lees A, Golbe LI, Williams DR, Corvol JC, Ludolph A, Burn D, Lorenzl S, Litvan I, Roberson ED, Höglinger GU, Koestler M, …
• From door-to-balloon time to contact-to-device time: predictors of achieving target times in patients with ST-elevation myocardial infarction.
  Clinical cardiology 2014 Roswell RO, Greet B, Parikh P, Mignatti A, Freese J, Lobach I, Guo Y, Keller N, Radford M, Bangalore S
• Periprocedural glycemic control in patients with diabetes mellitus undergoing coronary angiography with possible percutaneous coronary intervention.
  The American journal of cardiology 2014 Shah B, Berger JS, Amoroso NS, Mai X, Lorin JD, Danoff A, Schwartzbard AZ, Lobach I, Guo Y, Feit F, Slater J, Attubato MJ, Sedlis SP
• Application of quantitative DTI metrics in sporadic CJD.
  NeuroImage. Clinical 2014 Caverzasi E, Henry RG, Vitali P, Lobach IV, Kornak J, Bastianello S, Dearmond SJ, Miller BL, Rosen HJ, Mandelli ML, Geschwind MD
• Genotype-Based Association Mapping of Complex Diseases: Gene-Gene and Gene-Environment Interactions in Presence of Linkage Disequilibrium
  Statistics and Its Interface 2014 Lobach, I., Fan, R., Manga, P.
• Genotype-based association models of complex diseases to detect gene-gene and gene-environment interactions.
  Statistics and its interface 2014 Lobach I, Fan R, Manga P
• Handedness and language learning disability differentially distribute in progressive aphasia variants.
  Brain : a journal of neurology 2013 Miller ZA, Mandelli ML, Rankin KP, Henry ML, Babiak MC, Frazier DT, Lobach IV, Bettcher BM, Wu TQ, Rabinovici GD, Graff-Radford NR, Miller BL, Gorno-Tempini ML
• Modifiable risk factor burden and the prevalence of peripheral artery disease in different vascular territories.
  Journal of vascular surgery 2013 Berger JS, Hochman J, Lobach I, Adelman MA, Riles TS, Rockman CB
• Capgras syndrome in Dementia with Lewy Bodies.
  International psychogeriatrics 2012 Thaipisuttikul P, Lobach I, Zweig Y, Gurnani A, Galvin JE
• Mean platelet volume and long-term mortality in patients undergoing percutaneous coronary intervention.
  The American journal of cardiology 2012 Shah B, Oberweis B, Tummala L, Amoroso NS, Lobach I, Sedlis SP, Grossi E, Berger JS
• Effectiveness of smoking-cessation interventions for urban hospital patients: study protocol for a randomized controlled trial.
  Trials 2012 Grossman E, Shelley D, Braithwaite RS, Lobach I, Goffin A, Rogers E, Sherman S
• Very long-term clinical follow-up after fractional flow reserve-guided coronary revascularization.
  The Journal of invasive cardiology 2012 Miller LH, Toklu B, Rauch J, Lorin JD, Lobach I, Sedlis SP
• Inverse relationship between cirrhosis and massive tumours in hepatocellular carcinoma.
  HPB : the official journal of the International Hepato Pancreato Biliary Association 2012 Sarpel U, Ayo D, Lobach I, Xu R, Newman E
• Genotype-Based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors.
  Journal of probability and statistics 2012 Lobach I, Fan R
• Risk factors for early-onset and late-onset hepatocellular carcinoma in Asian immigrants with hepatitis B in the United States.
  The American journal of gastroenterology 2011 Wan DW, Tzimas D, Smith JA, Kim S, Araujo J, David R, Lobach I, Sarpel U
• Mechanisms of myocardial infarction in women without angiographically obstructive coronary artery disease.
  Circulation 2011 Reynolds HR, Srichai MB, Iqbal SN, Slater JN, Mancini GB, Feit F, Pena-Sing I, Axel L, Attubato MJ, Yatskar L, Kalhorn RT, Wood DA, Lobach IV, Hochman JS
• Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observations from traditional and bayesian random-effects meta-analyses of randomized trials.
  Circulation 2011 Bangalore S, Kumar S, Lobach I, Messerli FH
• Factors associated with frequent utilization of crisis substance use detoxification services.
  Journal of addictive diseases 2011 Carrier E, McNeely J, Lobach I, Tay S, Gourevitch MN, Raven MC
• Mexican urban occupational health in the US: a population at risk.
  Journal of community health 2011 Gany F, Dobslaw R, Ramirez J, Tonda J, Lobach I, Leng J
• Cancer portal project: a multidisciplinary approach to cancer care among Hispanic patients.
  Journal of oncology practice 2011 Gany F, Ramirez J, Nierodzick ML, McNish T, Lobach I, Leng J
• Semiparametric Bayesian analysis of gene-environment interactions with error in measurement of environmental covariates and missing genetic data.
  Statistics and its interface 2011 Lobach I, Mallick B, Carroll RJ
• Genotype-based association mapping of complex diseases: gene-environment interactions with multiple genetic markers and measurement error in environmental exposures.
  Genetic epidemiology 2010 Lobach I, Fan R, Carroll RJ
• Normal intima-media thickness on carotid ultrasound reliably excludes an ischemic cause of cardiomyopathy.
  American heart journal 2010 Reynolds HR, Steckman DA, Tunick PA, Kronzon I, Lobach I, Rosenzweig BP
• Haplotype-based regression analysis and inference of case-control studies with unphased genotypes and measurement errors in environmental exposures.
  Biometrics 2007 Lobach I, Carroll RJ, Spinka C, Gail MH, Chatterjee N
• Genotype-based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors
  Journal of Probability and Statistics Lobach, I and Fan, R