Search bioRxiv⌕ Search

Biology subjects

Mulligan, C. J.

Publications and source records attributed to Mulligan, C. J..

3 recordsLinked to original sources

Financial strain and stressful social environment drive depressive symptoms, while FKBP5 variant intensifies the effect, in African Americans living in Tallahassee

The World Health Organization estimates that almost 300 million people suffer from depression worldwide. Depression is the most common mental health disorder and shows racial disparities in disease prevalence, age of onset, severity of symptoms, frequency of diagnosis, and treatment utilization across the United States. Since depression has both social and genetic risk factors, we propose a conceptual model wherein social stressors are primary risk factors for depression, but genetic variants increase or decrease individual susceptibility to the effects of the social stressors. Our research strategy incorporates both social and genetic data to investigate variation in symptoms of depression (CES-D scores). We collected data on financial strain (difficulty paying bills) and personal social networks (a model of an individuals social environment), and we genotyped genetic variants in five genes involved in stress reactivity (HTR1a, BDNF, GNB3, SLC6A4, and FKBP5) in 135 African Americans residing in Tallahassee, Florida. We found that high financial strain and a high percentage of people in ones social network who are a source of stress or worry were significantly associated with higher CES-D scores and explained more variation in CES-D scores than did genetic factors. Only one genetic variant (rs1360780 in FKBP5) was significantly associated with CES-D scores and only when the social stressors were included in the model. Interestingly, the effect of FKPB5 appeared to be strongest in individuals with high financial strain such that participants with a T allele at rs1360780 in FKBP5 and high financial strain had the highest mean CES-D scores in our study population. These results suggest that material disadvantage and a stressful social environment increases the risk of depression, but that individual-level genetic variation may increase susceptibility to the adverse health consequences of social stressors.

genetics↗

FAAH, SLC6A4, and BDNF variants are not associated with psychosocial stress and mental health outcomes in a population of Syrian refugee youth

The developmental origins of health and disease (DOHaD) hypothesis posits that early childhood stressors disproportionately impact adult health. Numerous studies have found adult mental health to be associated with childhood adversities and genetic variants, particularly in genes related to neurochemistry. However, few studies have examined the way interactive effects may manifest over time and fewer still include protective factors, like resilience. Our group has previously found associations between the monoamine oxidase A gene, MAOA, and a contextually-specific measure of resilience with a measure of perceived psychosocial stress over time in Syrian refugee youth. In this study, we work with the same sample of adolescents to test genetic variants in three additional candidate genes (FAAH, the 5-HTTLPR region of SLC6A4, and BDNF) for associations with six psychosocial stress and mental health outcomes. Using multi-level modeling, we find no association between variants in these candidate genes and psychosocial stress or mental health outcomes. Our analysis included tests for both direct genetic effects and interactions with lifetime trauma and resilience. Negative results, such as the lack of genetic associations with outcome measures, provides a more complete framework in which to better understand positive results and associations.

genetics↗

Analyses of Neanderthal introgression suggest that Levantine and southern Arabian populations have a shared population history

ObjectivesModern humans are thought to have interbred with Neanderthals in the Near East soon after modern humans dispersed out of Africa. This introgression event likely took place in either the Levant or southern Arabian depending on which dispersal route out of Africa was followed. In this study, we compare Neanderthal introgression in contemporary Levantine and southern Arabian populations to investigate Neanderthal introgression and to study Near Eastern population history.\n\nMaterials and MethodsWe analyzed genotyping data on >400,000 autosomal SNPs from seven Levantine and five southern Arabian populations and compared those data to populations from around the world including Neanderthal and Denisovan genomes. We used f4 and D statistics to estimate and compare levels of Neanderthal introgression between Levantine, southern Arabian, and comparative global populations. We also identified 1,581 putative Neanderthal-introgressed SNPs within our dataset and analyzed their allele frequencies as a means to compare introgression patterns in Levantine and southern Arabian genomes.\n\nResultsWe find that Levantine and southern Arabian populations have similar levels of Neanderthal introgression to each other but lower levels than other non-Africans. Furthermore, we find that introgressed SNPs have very similar allele frequencies in the Levant and southern Arabia, which indicates that Neanderthal introgression is similarly distributed in Levantine and southern Arabian genomes.\n\nDiscussionWe infer that the ancestors of contemporary Levantine and southern Arabian populations received Neanderthal introgression prior to separating from each other and that there has been extensive gene flow between these populations.

genomics↗