Kuwaiti population subgroup of nomadic Bedouin ancestry—Whole genome sequence and analysis

AbstractKuwaiti native population comprises three distinct genetic subgroups of Persian, “city-dwelling” Saudi Arabian tribe, and nomadic “tent-dwelling” Bedouin ancestry. Bedouin subgroup is characterized by presence of 17% African ancestry; it owes it origin to nomadic tribes of the deserts of Arabian Peninsula and North Africa. By sequencing whole genome of a Kuwaiti male from this subgroup at 41X coverage, we report 3,752,878 SNPs, 411,839 indels, and 8451 structural variations. Neighbor-joining tree, based on shared variant positions carrying disease-risk alleles between the Bedouin and other continental genomes, places Bedouin genome at the nexus of African, Asian, and European genomes in concordance with geographical location of Kuwait and Peninsula. In congruence with participant's medical history for morbid obesity and bronchial asthma, risk alleles are seen at deleterious SNPs associated with obesity and asthma. Many of the observed deleterious ‘novel’ variants lie in genes associated with autosomal recessive disorders characteristic of the region

Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases

Background: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance. Methods: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins. Results: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F). Conclusion: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases

Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases

BACKGROUND: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance.METHODS: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins.RESULTS: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F).CONCLUSION: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases.</p

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies

Enhancement of integrated circuits performance : metal gate electrodes and strained silicon MOSFETs

Enhancement of the Metal Oxide Semiconductor Field Effect Transistor (MOSFET) device performance has been achieved by work function engineering of Metal gates (controlling and lowering threshold Voltage (VTH)) and incorporating Strained Silicon as a substrate (higher mobility of the carriers). However there has not been any report on successful demonstration of low work function MOS Metal Gate Electrode and reliability of MOS Strained SOI devices. The thesis investigates a novel approach of tuning the work function of thermally stable Tantalum Nitride (TaN) metal gate using a Gadolinium buffer layer on Hafnium based high-k gate dielectrics. An NMOS compatible low work function metal gate resulting in lower VTH, has been successfully demonstrated. The thesis also explores the Bias Temperature Instability (BTI reliability) of the Strained Silicon on Insulator (S-SOI) MOSFETs for the first time. Degraded Reliability has been observed on strained devices and a plausible mechanism has been proposed.Electrical and Computer Engineerin

Genotyping-by-sequencing identifies date palm clone preference in agronomics of the State of Qatar.

Understanding the genetic diversity in a crop population is key to its targeted breeding for desired traits, such as higher yields, better fruit quality and resistance to disease and changing climates. Date fruits represent a major crop in the Middle East and are key to achieving future food independence in arid countries like Qatar. We previously determined the genome of the date palm Phoenix dactylifera and showed that date palm trees world-wide divide into two distinct subpopulations of Eastern and Western origins. Here we applied a resource of SNPs from 179 commercially available date fruits to assess the genetic diversity of date palm trees grown in the State of Qatar. We found that palm trees in Qatar are mainly of Eastern origin, and that their genetic diversity doesn't associate with regions of the State. Together with targeted genetic assays, our resource can be used in the future for date palm cultivar identification, to aid selecting suitable cultivars for targeted breeding, to improve a country's date palm genetic diversity, and to certify the origin of date fruits and trees