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Ramachandran, V. S.

Publications and source records attributed to Ramachandran, V. S..

3 recordsLinked to original sources

Genetic Architecture and Analysis Practices of Circulating Metabolites in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program

Circulating metabolite levels partly reflect the state of human health and diseases and can be impacted by genetic determinants. Hundreds of loci associated with circulating metabolites have been identified; however, most findings focus on predominantly European ancestry or single-study analyses. Leveraging the rich metabolomics resources generated by the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program, we harmonized and accessibly cataloged 1,729 circulating metabolites among 25,058 ancestrally diverse samples. We provided a set of reasonable strategies for outlier and imputation handling to process metabolite data. Following the practical analysis framework, we further performed a genome-wide association analysis on 1,135 selected metabolites using whole genome sequencing data from 16,359 individuals passing the quality control filters, and discovered 1,778 independent loci associated with 667 metabolites. Among 108 novel locus-metabolite pairs, we detected not only novel loci within previously implicated metabolite associated genes but also novel genes (such as GAB3 and VSIG4 located in the X chromosome) that have putative roles in metabolic regulation. In the sex-stratified analysis, we revealed 85 independent locus-metabolite pairs with evidence of sexual dimorphism, including well-known metabolic genes such as FADS2, D2HGDH, SUGP1, UTG2B17, strongly supporting the importance of exploring sex difference in the human metabolome. Taken together, our study depicted the genetic contribution to circulating metabolite levels, providing additional insight into the understanding of human health.

bioinformatics↗

Context influences how individuals with misophonia respond to sounds

Misophonia is a newly researched condition in which specific sounds cause an intense, aversive response in individuals, characterized by negative emotions and autonomic arousal. Although virtually any sound can become a misophonic "trigger," the most common sounds appear to be bodily sounds related to chewing and eating as well as other repetitive sounds. An intriguing aspect of misophonia is the fact that many misophonic individuals report that they are triggered more, or even only, by sounds produced by specific individuals, and less, or not at all, by sounds produced by animals (although there are always exceptions). In general, anecdotal evidence suggests that misophonic triggers involve a combination of sound stimuli and contextual cues. The aversive stimulus is more than just a sound and can be thought of as a Gestalt of features which includes sound as a necessary component as well as additional contextual information. In this study, we explore how contextual information influences misophonic responses to human chewing, as well as sonically similar sounds produced by non-human sources. The current study revealed that the exact same sound can be perceived as being much more or less aversive depending on the contextual information presented alongside the auditory information. The results of this study provide a foundation for potential cognitive based therapies.

neuroscience↗

Modulation of Body Mass Composition using Vestibular Nerve Stimulation.

There is increasing evidence of a \"set-point\" for body weight in the brain, that is regulated by the hypothalamus. This system modifies feeding behavior and metabolic rate, to keep body fat within predetermined parameters. It is also known that animals subjected to chronic centrifugation show a reduction in body fat. Experiments with mutant mice found that this loss of fat appears to be mediated by a vestibulo-hypothalamic pathway. Vestibular nerve stimulation (VeNS), also known as galvanic vestibular stimulation, involves non-invasively stimulating the vestibular system by applying a small electrical current between two electrodes placed over the mastoid processes. We suggest that any means of repeatedly stimulating the otolith organs in humans would cause a reduction in total body fat, and that VeNS would be a useful technique to use in this regard. Below we provide pilot data to support this idea.

neuroscience↗