Biology subjects

Avinun, R.

Publications and source records attributed to Avinun, R..

3 recordsLinked to original sources

bioRxiv2019

A Polygenic Score for Body Mass Index is Associated with Depressive Symptoms via Early Life Stress: Evidence for Gene-Environment Correlation

BackgroundIncreasing childhood overweight and obesity rates are associated with not only adverse physical, but also mental health outcomes, including depression. These negative outcomes may be caused and/or exacerbated by the bullying and shaming overweight individuals experience. As body mass index (BMI) can be highly heritable, we hypothesized that a genetic risk toward higher BMI, will predict higher early life stress (ELS), which in turn will predict higher depressive symptoms in adulthood. Such a process will reflect an evocative gene-environment correlation (rGE) wherein an individuals genetically influenced phenotype evokes a reaction from the environment that subsequently shapes the individuals health. MethodsWe modeled genetic risk using a polygenic score of BMI derived from a recent large GWAS meta-analysis. Self-reports were used for the assessment of ELS and depressive symptoms in adulthood. The discovery sample consisted of 524 non-Hispanic Caucasian university students from the Duke Neurogenetics Study (DNS; 278 women, mean age 19.78{+/-}1.23 years) and the independent replication sample consisted of 5 930 white British individuals from the UK biobank (UKB; 3 128 women, mean age 62.66{+/-}7.38 years). ResultsA significant mediation effect was found in the DNS (indirect effect=.207, bootstrapped SE=.10, 95% CI: .014 to .421), and then replicated in the UKB (indirect effect=.04, bootstrapped SE=.01, 95% CI: .018 to .066). Higher BMI polygenic scores were associated with higher depressive symptoms through the experience of higher ELS. ConclusionsOur findings suggest that evocative rGE may contribute to weight-related mental health problems and stress the need for interventions that aim to reduce weight bias, specifically during childhood.

genetics↗

bioRxiv2019

A GWAS-Derived Polygenic Score for Interleukin-1β is Associated with Hippocampal Volume in Two Samples

Accumulating research suggests that the pro-inflammatory cytokine interleukin-1{beta} (IL-1{beta}) has a modulatory effect on the hippocampus, a brain structure important for learning and memory as well as linked with both psychiatric and neurodegenerative disorders. Here, we use an imaging genetics strategy to test an association between an IL-1{beta} polygenic score, derived from summary statistics of a recent genome-wide association study (GWAS) of circulating cytokines, and hippocampal volume, in two independent samples. In the first sample of 512 non-Hispanic Caucasian university students (274 women, mean age 19.78 {+/-} 1.24 years) from the Duke Neurogenetics Study, we identified a significant positive correlation between higher polygenic scores, which presumably reflect higher circulating IL-1{beta} levels, and average hippocampal volume. This positive association was successfully replicated in a second sample of 7,960 white British volunteers (4,158 women, mean age 62.63{+/-}7.45 years) from the UK Biobank. Collectively, our results suggest that a functional GWAS-derived score of IL-1{beta} blood circulating levels affects hippocampal volume, and lend further support in humans, to the link between IL-1{beta} and the structure of the hippocampus.

neuroscience↗

bioRxiv2019

Genetic Risk for Rheumatoid Arthritis is Associated with Increased Striatal Volume in Healthy Young Adults

Rheumatoid arthritis (RA), an autoimmune disease, has recently been associated with increased striatal volume and decreased intracranial volume (ICV) in longstanding patients. As inflammation has been shown to precede the clinical diagnosis of RA and it is a known moderator of neuro- and gliogenesis, we were interested in testing whether these brain morphological changes appear before the clinical onset of disease in healthy young adult volunteers, as a function of relative genetic risk for RA. Genetic and structural MRI data were available for 516 healthy non-Hispanic Caucasian university students (275 women, mean age 19.78{+/-}1.24 years). Polygenic risk scores were computed for each individual based on a genome-wide association study of RA, so that higher scores indicated higher risk. Striatal volume (sum of caudate, putamen, and nucleus accumbens volumes) and ICV were derived for each individual from high-resolution T1-weighted images. After controlling for sex, age, genetic components of ethnicity, socioeconomic status, and depressive symptoms, we found that higher RA polygenic risk scores were associated with increased striatal volume, but not decreased ICV. Our findings suggest that increased striatal volume may be linked to processes that precede disease onset, such as inflammation, while decreased ICV may relate to disease progression.

neuroscience↗