Interaction Between Genetics, Environment, and Behavior and Health Outcomes

Notterman's group recently showed that women with a short, hypomorphic form of the promotor region of HTT (serotonin transporter) are more likely to experience post-partum depression in stressful socioeconomic circumstances then they are in more stable environments. However, women with the major allele of this gene (long promotor) do not display this environment-based difference in rate of postpartum depression. This is consistent with the idea that some gene variants express proteins that enhance an organism's sensitivity to the environment—so called "reactive alleles."

It is also known that variations in environmental input induce longstanding behavioral changes by affecting the methylation state of DNA. There is great excitement around these sorts of findings because it points the way to a biological understanding—invoking epigenetic mechanisms—of the relationship between adverse or favorable early environments and lifelong behavioral traits.

Notterman's lab is engaging these issues through several collaborations with social scientists and pediatricians. The lab serves as the genomics/epigenomics resource for the Future of Families and Child Wellbeing Study (FFCWS), based at the Princeton School of Public and International Affairs. The FFCWS is following a cohort of nearly 5,000 children born in large U.S. cities between 1998 and 2000 (roughly three-quarters of whom were born to unmarried parents). The study is in its 22nd year, and we have collected DNA from participants at year 9, 15, and now 22. This enables us to make detailed correlations between genetic and epigenetic states and social, behavioral, health, and demographic data.

Using this information, his group recently showed that adverse early environments are associated with accelerated loss of telomeres by age 9 years, and that the extent of loss is moderated by genetic variants in serotonergic pathways. This is again consistent with the hypothesis that the products of these genes modulate the organism's environmental sensitivity and was featured in a commentary in Nature. Since early life telomere length is associated with both adult health and with lifespan, this research suggests a mechanism for the known effect of social disparity on wellbeing throughout the lifespan.

Major projects include the comprehensive genotyping of more than 7500 DNA samples from the FFCWS cohort (mothers and children). Accompanying this project is a complementary effort to measure the methylation of DNA CpG sites. At a more mechanistic level, his group is trying to understand the biological mechanism that seems to link telomere erosion to stress.

Cytomegalovirus and Telomeres

Social Isolation in Drosophila

Genetics of Autism

Notterman's group has developed a cohort of families in which more than one sibling has an autism spectrum disorder. We have analyzed whole genome sequence data, as well as exam and methylation data on monozygotic and dizygotic twins (and their parents and siblings), some of whom have discordant phenotypes. This will enable us to make detailed correlations between the autistic phenotype and various genetic and epigenetic abnormalities.