Laboratory for Genetic Epidemiology

My research integrates classical and innovative statistical approaches (i.e., linkage analysis, case-control analysis, genome-wide association analysis, whole exome/genome sequencing) to comprehensively characterize the genetic basis of normal aging and age-associated neurodegenerative diseases/disabilities. By conducting research on ethnically diverse family, population, and community-based cohorts, my research aims are to obtain a better understanding of the existing ethnic disparities in cognitive impairment and neurodegenerative disorders. I also serves as a statistical geneticist in a diverse number of large multicenter initiatives, including the Alzheimer’s Disease Sequencing Project, The Long-Life Family Study, and the NIA-LOAD Family Study, and the Alzheimer’s Disease Genetics Consortium, among others.

My group studies the genetics of Alzheimer’s disease by focusing on cohorts with known genetic risk factors, including families with at least one person carrying a mutation in the PSEN1 gene; and adults with Down syndrome who carry three copies of the APP gene. These high-risk individuals display a surprisingly wide range of clinical expression. For example, the age at onset of AD can vary by more than two decades among family members who carry the same PSEN1 mutation. Similarly, some adults with Down syndrome can survive into their 70s without dementia. We ask how some individuals manage to escape AD into old age. To better understand the biological processes at the molecular level, we examine their genome along with biomarkers. In addition, we study the other extreme by studying families with multiple family members surviving to old age without major disease.

My research focuses on the identification of genetic factors associated with Alzheimer's disease in non-Hispanic White and minority populations through integration of a variety of epidemiological, clinical, and genomic methodologies. Working closely with the Alzheimer’s Disease Genetics Consortium and the Alzheimer’s Disease Sequencing Project, major current studies include large-scale sequencing projects of multiplex families and Singleton individuals of African ancestry with Alzheimer’s Disease, and ascertainment, sequencing, and genomic analysis of multiplex families and Singleton individuals affected by non-Mendelian early-onset Alzheimer’s disease.

I am a bioinformatician by training, and my primary interests are to understand the role of genetic variation in the biology of neurodegenerative diseases, in particular, Alzheimer’s disease. I have extensive experience in designing, implementing, and analyzing next generation sequencing studies. In parallel, I am also interested in implementing computational approaches to gene discovery in AD. My team is involved in several multi-institutional studies of genetics of AD including the Alzheimer’s Disease Sequencing Project and Collaboration on Alzheimer’s Disease Research. We are applying computational pipelines to characterize structural variation in large scale sequencing data for gene discovery in Alzheimer’s disease. I also lead multiomics integration of genetic, transcriptomic, proteomic, metabolomics data for gene and pathway discovery in multiple cohorts including the EFIGA (Caribbean-Hispanic families) and WHICAP (Washington Heights-Inwood Columbia Aging Project).