Dr. Iryna V. Lobach conducts research in applied statistics and supports the biostatistics component of biomedical research.

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.

Recently, 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 to correct the bias and apply the methods to large genome-wide studies of Prostate Cancer and Alzheimer’s disease.

We derived a simple approximation to bias in GxE estimates when multiple distinct disease states share a clinical diagnosis(http://biorxiv.org/cgi/content/short/444588v1, https://www.biorxiv.org/content/early/2018/11/29/483198) and when substantial fractions of controls are in fact undiagnosed cases (https://www.biorxiv.org/content/early/2018/10/17/444596).

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).