Ravindranath Duggirala
A5031109876- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Genetic Mapping and Diversity in Plants and Animals
- Bioinformatics and Genomic Networks
- Liver Disease Diagnosis and Treatment
- Genetic and phenotypic traits in livestock
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Nutrition, Genetics, and Disease
- Peroxisome Proliferator-Activated Receptors
- Epigenetics and DNA Methylation
- Birth, Development, and Health
- Cardiovascular Disease and Adiposity
- Metabolomics and Mass Spectrometry Studies
- Chronic Kidney Disease and Diabetes
- Lipid metabolism and disorders
- Genomic variations and chromosomal abnormalities
- Advanced Neuroimaging Techniques and Applications
- Cancer-related gene regulation
- Diet and metabolism studies
- Regulation of Appetite and Obesity
- Obesity, Physical Activity, Diet
- Diabetes and associated disorders
Texas A&M University – San Antonio
2023-2025
The University of Texas Rio Grande Valley
2015-2025
Texas Biomedical Research Institute
2011-2023
Texas Diabetes Institute
2015-2019
Hershey (United States)
2019
The University of Texas Health Science Center at San Antonio
1997-2016
Brownsville Public Library
2016
The University of Texas System
2015
Albert Einstein College of Medicine
2010
Yale University
2009
Abstract Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences gene disruption: crucial for function an organism will be depleted such in natural populations, whereas non-essential tolerate their accumulation. However, predicted loss-of-function enriched annotation errors, and tend to found at extremely low frequencies, so analysis requires careful variant very large sample sizes 1 . Here we describe aggregation 125,748...
Tobacco and alcohol use are heritable behaviours associated with 15% 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease injury1-4. These substances used across the globe, yet genome-wide association studies have focused on individuals European ancestries5. Here we leveraged global genetic diversity 3.4 million from four major clines ancestry (approximately 21% non-European) power discovery fine-mapping genomic loci tobacco use, inform function these via...
Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations rare (with minor allele frequencies less than 0.5%) in 4 genes at exome-wide significance, including a series more 30 SLC30A8 alleles conveys protection against T2D, 12 gene sets, those...
Abstract Naturally occurring human genetic variants that are predicted to inactivate protein-coding genes provide an in vivo model of gene inactivation complements knockout studies cells and organisms. Here we report three key findings regarding the assessment candidate drug targets using loss-of-function variants. First, even essential genes, which not tolerated, can be highly successful as inhibitory drugs. Second, most sufficiently rare genotype-based ascertainment homozygous or compound...
Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories these data seek to be disease-agnostic therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is public resource datasets genomic annotations dedicated type diabetes (T2D) related traits. Here, we make the T2DKP more accessible prospective users useful existing users. First, evaluate T2DKP's comprehensiveness by comparing its with...
Insulin resistance syndrome (IRS)−related phenotypes, such as hyperinsulinemia, obesity-related traits, impaired glucose tolerance, dyslipidemia, and hypertension, tend to cluster into factors. We attempted identify loci influencing the factors of IRS-related phenotypes using phenotypic data from 261 nondiabetic subjects distributed across 27 low-income Mexican-American extended families. Principal component factor analyses were performed eight phenotypes: fasting (FG), specific insulin...
Upstream open reading frames (uORFs) are tissue-specific cis-regulators of protein translation. Isolated reports have shown that variants create or disrupt uORFs can cause disease. Here, in a systematic genome-wide study using 15,708 whole genome sequences, we show new upstream start codons, and disrupting stop sites existing uORFs, under strong negative selection. This selection signal is significantly stronger for arising genes intolerant to loss-of-function variants. Furthermore, creating...
Inferring relatedness from genomic data is an essential component of genetic association studies, population genetics, forensics, and genealogy. While numerous methods exist for inferring relatedness, thorough evaluation these approaches in real has been lacking. Here, we report assessment 12 state-of-the-art pairwise inference using a set with 2485 individuals contained several large pedigrees that span up to six generations. We find all have high accuracy (92-99%) when detecting first-...
Abstract Human genetic variants predicted to cause loss-of-function of protein-coding genes (pLoF variants) provide natural in vivo models human gene inactivation and can be valuable indicators function the potential toxicity therapeutic inhibitors targeting these 1,2 . Gain-of-kinase-function LRRK2 are known significantly increase risk Parkinson’s disease 3,4 , suggesting that inhibition kinase activity is a promising strategy. While preclinical studies model organisms have raised some...
Abstract Hundreds of thousands genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops disease (termed penetrance) is unknown for virtually all them. Additionally, clinical utility common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral type 2 diabetes case-control study and 38,566 participants UK Biobank, whom genotype array data were also available), we...
Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, interpretation clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M were not...
Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide study (GWAS) summary statistics, whole-genome sequences expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative using an optimal linear combination of statistics), to integrate eQTL dataset with multi-ancestry GWAS. By exploiting shared phenotypic effects...
Type 2 diabetes (T2D) etiology is highly complex due to its multiple roots of origin. Polygenic risk scores (PRS) based on genome-wide association studies (GWAS) can partially explain T2D risk. Asian Indian people have up six times higher developing than European people, and underlying causes this disparity are unknown. We performed targeted sequencing ten GWAS/candidate regions using endogamous Punjabi Sikh families replication unrelated from three other ethnic groups (EEGs). detect rare...