Biology subjects

Grover, S.

Publications and source records attributed to Grover, S..

3 recordsLinked to original sources

bioRxiv2018

Risky behaviors and Parkinson’s disease: A Mendelian randomization study in up to 1 million study participants

ObjectiveDopaminergic neurotransmission is known to be a potential modulator of risky behaviors including substance abuse, promiscuity, and gambling. Furthermore, observational studies have shown associations between risky behaviors and Parkinsons disease; however, the causal nature of these associations remains unclear. Thus, in this study, we examine causal associations between risky behavior phenotypes on Parkinsons disease using a Mendelian randomization approach.\n\nMethodsWe used two-sample Mendelian randomization to generate unconfounded estimates using summary statistics from two independent, large meta-analyses of genome-wide association studies on risk taking behaviors (n=370,771-939,908) and Parkinsons disease (cases: n=9581, controls: n = 33,245). We used inverse variance weighted as the main method for judging causality.\n\nResultsOur results support a strong protective association between the tendency to smoke and Parkinsons disease (OR=0.714 per log odds of ever smoking; 95% CI=0.568-0.897; p-value=0.0041; Cochran Q test; p-value=0.238; I2 index=6.3%). Furthermore, we observed risk association trends between automobile speed propensity as well as the number of sexual partners and Parkinsons disease after removal of overlapping loci with other risky traits (OR=1.986 for each standard deviation increase in normalized automobile speed propensity; 95% CI=1.215-3.243; p-value=0.0066, OR=1.635 for each standard deviation increase in number of sexual partners; 95% CI=1.165-2.293; p-value=0.0049).\n\nInterpretationThese findings provide support for a causal relationship between general risk tolerance and Parkinsons disease and may provide new insights in the pathogenic mechanisms leading to the development of Parkinsons disease.

genetics↗

bioRxiv2017

Sensory and decisional components of endogenous attention are dissociable.

Endogenously cueing a stimulus for attention enhances sensory processing of the attended stimulus, and efficiently selects information from the attended stimulus for guiding behavioral decisions. Yet, it is unknown if these sensory and decisional components of endogenous attention are under the control of common, overlapping or distinct mechanisms. Here, we tested human observers in a multi-alternative visuospatial attention task with probabilistic spatial cues, whose predictive validity varied across spatial locations. Observers behavioral choices were analyzed with a multidimensional signal detection model, derived from Bayesian decision theory. The model effectively decoupled attentions effects on perceptual sensitivity from those on decisional thresholds (bias), and revealed striking dissociations between them. Sensitivity was highest at the cued location, and not significantly different among uncued locations, suggesting a spotlight-like allocation of sensory resources at the cued location. On the other hand, bias varied systematically with endogenous cue validity, suggesting a graded distribution of decision thresholds across all locations. Cueing-induced modulations of sensitivity and bias were uncorrelated within and across subjects. Finally, bias selectively correlated with key measures of decision-making: reaction times were strongly correlated with bias, cueing-induced benefits in reaction times were correlated with bias changes independently of sensitivity changes, and subjects who exhibited higher bias, rather than higher sensitivity, toward the cued location produced more optimal behavioral decisions. Our model and findings demonstrate that endogenous cueing of attention does not engage a unitary selection mechanism, but rather involves the operation of dissociable sensory enhancement and decisional selection processes.\n\nSignificance statementThe capacity for selective attention allows us to engage efficiently with the most important objects in the world around us. Attention affects the way we perceive important stimuli and also affects how we make behavioral decisions about these stimuli. In this study, we test human observers on a multiple alternative attention task and show that attentions effects on perceptual processing and decision-making can be dissociated. Specifically, attentions sensory effects alone are in line with the conventional notion of an attentional \"spotlight\". These insights are obtained with a novel Bayesian decision model, which we propose as a powerful tool for teasing apart component processes of cognitive phenomena, and could aid the search for the neural correlates of these phenomena.

neuroscience↗

bioRxiv2017

Cis-regulatory evolution integrated the Bric-a-brac transcription factors into a novel fruit fly gene regulatory network

Gene expression evolution through gene regulatory network (GRN) changes has gained appreciation as a driver of morphological evolution. However, understanding how GRNs evolve is hampered by finding relevant cis-regulatory element (CRE) mutations, and interpreting the protein-DNA interactions they alter. We investigated evolutionary changes in the duplicated Bric-a-brac (Bab) transcription factors and a key Bab target gene in a GRN underlying the novel dimorphic pigmentation of D. melanogaster and its relatives. It has remained uncertain how Bab was integrated within the pigmentation GRN. Here we show that Bab gained a role in sculpting sex-specific pigmentation through the evolution of binding sites in a CRE of the pigment-promoting yellow gene and without any noteworthy changes to Bab protein coding sequences. This work demonstrates how a new trait can evolve by incorporating existing transcription factors into a GRN through CRE evolution, an evolutionary path likely to predominate newly evolved functions of transcription factors.

genetics↗