Publications by authors named "Alyna Khan"
Background: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear.
Method And Results: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program.
Article Synopsis
- Polygenic risk scores (PRSs) could enhance disease risk prediction, but their current effectiveness is compromised for non-European populations, creating potential health disparities.
- The PRIMED Consortium aims to improve PRS performance by aggregating diverse genetic data on a cloud platform and evaluating ethical implications related to its implementation.
- Focused on cardiometabolic diseases and cancer, PRIMED seeks to promote equity in polygenic risk assessment through collaboration across multiple research sites and organizations.
Objectives: Our study assesses the current knowledge and prior awareness of undergraduate medical students in Pakistan regarding palliative care.
Study Design: This descriptive Cross-sectional online survey was distributed among undergraduate medical students across Pakistan, with a sample size of 246 participants. The questionnaire, adapted from the PaCKS questionnaire by Kozlov et al.
Article Synopsis
- - A rare genetic condition involving mitochondrial complex III deficiency and lactic acidosis, characterized by scalp alopecia, was identified in two unrelated cases and discussed further with a participant from the Undiagnosed Diseases Network (UDN).
- - The participant had two autosomal recessive disorders discovered through genome sequencing: mitochondrial complex III deficiency and cataracts, with specifics on previously documented pathogenic variants for each condition.
- - A combination of enzyme assays and cellular proteomics showed clear dysfunction in complex III and low levels of a crucial protein, validating the genetic mutations' pathogenic effects and broadening understanding of these rare disorders.
Article Synopsis
- Whole genome sequencing (WGS) helps identify rare genetic variants that may explain the missing heritability of coronary artery disease (CAD) by analyzing 4,949 cases and 17,494 controls from the NHLBI TOPMed program.
- The study estimates that the heritability of CAD is around 34.3%, with ultra-rare variants contributing about 50%, especially those with low linkage disequilibrium.
- Functional annotations show significant enrichment of CAD heritability, highlighting the importance of ultra-rare variants and specific regulatory mechanisms in different cells as major factors influencing genetic risk for the disease.
Article Synopsis
- Clonal hematopoiesis (CH) occurs when genetically identical blood cells expand, often influenced by genetic mutations linked to blood cancers; however, many cases happen without known driver mutations.
- Researchers analyzed 51,399 genomes to study a specific type of CH (CH-LPMneg) without detectable leukemia-related mutations, developing a new method (GEM rate) to estimate mutation burden without paired samples.
- Through their study, they identified seven genes linked to CH-LPMneg and found that alterations in hematopoietic stem cell (HSC) behavior may drive this mutation burden, while a broader analysis revealed relationships between GEM and the expression of 404 genes.
Article Synopsis
- Coronary artery calcification (CAC) is linked to heart disease and assessed through a genome-wide association study (GWAS) involving 22,400 participants from various backgrounds.
- The study confirmed connections with four known genetic loci and discovered two new loci related to CAC, with supportive replication findings for both.
- Functional tests suggest that ARSE promotes calcification in vascular smooth muscle cells and its variants may influence CAC levels, identifying ARSE as a key target for potential treatments in vascular calcific diseases.
Background: Birth injury or birth trauma refers to physical damage or trauma that occurs to a newborn during the birthing process. To ensure continuous care and improve neonatal outcomes, it is crucial to know the incidence, types, relation to the mode of delivery, and their management.
Methodology: This is a retrospective cohort study conducted at Aga Khan University Hospital, Pakistan from January 2018 to December 2022.
Article Synopsis
- The study investigates the role of CCR2, a receptor for CCL2 involved in monocyte movement, in the risk of atherosclerotic cardiovascular disease, particularly through examining genetic variants in a large population sample from the UK Biobank.
- Researchers identified 45 harmful genetic variants linked to lower monocyte counts, finding that carriers had a reduced risk of myocardial infarction and coronary artery disease, especially the M249K variant.
- The M249K variant was associated with significantly lower risks for heart issues without increasing infection risk, suggesting its potential protective role against cardiovascular diseases.
Objectives: Transcript sequencing of patient-derived samples has been shown to improve the diagnostic yield for solving cases of suspected Mendelian conditions, yet the added benefit of full-length long-read transcript sequencing is largely unexplored.
Methods: We applied short-read and full-length transcript sequencing and mitochondrial functional studies to a patient-derived fibroblast cell line from an individual with neuropathy that previously lacked a molecular diagnosis.
Results: We identified an intronic homozygous c.
With the introduction of next generation sequencing (NGS) technology in the forensic field, it will be of interest to assess if forensic scientists feel equipped to interpret and present DNA evidence for sequence data. Here, we describe perceptions of sixteen U.S.
View Article and Find Full Text PDFArticle Synopsis
- The study evaluates the effectiveness and shortcomings of polygenic risk scores (PRSs) in predicting various blood pressure (BP) phenotypes among different population groups, focusing on methods like "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2).
- It utilizes datasets from several biobanks, including MGB Biobank and UK Biobank, to train and validate PRSs based on self-reported race/ethnic backgrounds such as Asian, Black, Hispanic/Latino, and White.
- Findings indicate that the PRS-CSx method, which combines weighted PRSs from multiple GWAS, provides the most accurate predictions across all racial/ethnic groups, with better effectiveness in females
Objectives: Transcript sequencing of patient derived samples has been shown to improve the diagnostic yield for solving cases of likely Mendelian disorders, yet the added benefit of full-length long-read transcript sequencing is largely unexplored.
Methods: We applied short-read and full-length isoform cDNA sequencing and mitochondrial functional studies to a patient-derived fibroblast cell line from an individual with neuropathy that previously lacked a molecular diagnosis.
Results: We identified an intronic homozygous c.
How race, ethnicity, and ancestry are used in genomic research has wide-ranging implications for how research is translated into clinical care and incorporated into public understanding. Correlation between race and genetic ancestry contributes to unresolved complexity for the scientific community, as illustrated by heterogeneous definitions and applications of these variables. Here, we offer commentary and recommendations on the use of race, ethnicity, and ancestry across the arc of genetic research, including data harmonization, analysis, and reporting.
View Article and Find Full Text PDFBackground: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.
Methods: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.
Article Synopsis
- - Human genetic studies show that shorter leukocyte telomere length (LTL) is linked to a higher risk of coronary artery disease (CAD), while the relationship between LTL and various cancers is less clear.
- - Clonal hematopoiesis of indeterminate potential (CHIP), which involves the growth of blood cells with certain mutations, increases the risk for both blood cancers and CAD, with telomerase reverse transcriptase being a key genetic factor in CHIP.
- - Research from the TOPMed program and UK Biobank reveals that longer genetically predicted LTL increases the likelihood of developing CHIP, which then leads to a decrease in measured LTL, providing insights into how these factors might contribute to CAD prevention.
Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples.
View Article and Find Full Text PDFArticle Synopsis
- Genotype-phenotype association studies improve statistical power by combining phenotype data from multiple research efforts, but data harmonization poses challenges due to varying definitions and methods.
- A centralized harmonization system was developed for the National Heart, Lung, and Blood Institute's TOPMed program, successfully standardizing 63 phenotypes from studies conducted between 1948 and 2012.
- The harmonized data, along with documentation and software for future harmonization, have been shared with NIH data repositories, promoting collaboration and reproducibility in scientific research.
Article Synopsis
- A study involving over 65,000 participants analyzed genetic variations on the X chromosome and their impact on blood lipids, revealing significant associations with lower cholesterol levels.
- The research identified Xq23 region alleles that not only lower cholesterol and triglycerides but are also linked to reduced risk of coronary heart disease and type 2 diabetes.
- Additionally, while there was a relation to higher body mass index (BMI), adjustments showed that certain fat distributions are healthier, suggesting a complex relationship between fat, gene expression, and blood lipids.
Large-scale whole-genome sequencing studies have enabled the analysis of rare variants (RVs) associated with complex phenotypes. Commonly used RV association tests have limited scope to leverage variant functions. We propose STAAR (variant-set test for association using annotation information), a scalable and powerful RV association test method that effectively incorporates both variant categories and multiple complementary annotations using a dynamic weighting scheme.
View Article and Find Full Text PDF