Publications by authors named "Cristen Willer"
Article Synopsis
- - The study investigates the role of genetics in postoperative nausea and vomiting (PONV), which impacts patient satisfaction and results in unplanned hospital admissions after surgery, hypothesizing that genetic factors might explain some of the variability in risk that traditional factors do not cover.
- - Researchers conducted a genome-wide association study using data from patients at Michigan Medicine and Vanderbilt University Medical Center, identifying 46 genetic variants associated with PONV and developing a polygenic risk score to better predict occurrences in different patient cohorts.
- - Findings showed that higher polygenic risk scores corresponded with increased risk for developing PONV, suggesting that genetic predisposition combined with known clinical risks can improve understanding and prediction of this complication in surgical patients.
Article Synopsis
- Trace elements play a crucial role in human health but can also be toxic; their absorption and effects are influenced by genetics, but this area is still under-researched.
- This study conducted genome-wide analysis on 57 trace elements using blood samples from Scandinavian individuals, identifying 11 new genetic locations linked to the levels of specific elements such as arsenic, zinc, and selenium.
- The findings suggest some trace elements may have weak to moderate health impacts, with notable indications of increased zinc potentially being harmful and linked to prostate cancer, though more validation is required.
Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related.
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- Familial hypercholesterolemia (FH) is a genetic condition linked to high LDL cholesterol levels and increased risk of early coronary heart disease (CHD), though its effects on CHD in those with moderate LDL-C levels are not fully understood.
- * This study evaluated the CHD risk from FH variants in individuals with both moderately and severely elevated LDL-C levels and estimated the additional deaths from CHD related to FH in U.S. adults.
- * Among 21,426 participants, those with FH variants had significantly higher rates of developing CHD, with hazard ratios of 2.9 for those with moderately elevated LDL-C and 2.6 for those with severely elevated LDL-C.
Article Synopsis
- A genome-wide association study was conducted on thyroid function, analyzing data from up to 271,040 European individuals, focusing on hormones like TSH, FT4, and T3.
- The study identified 259 significant genetic associations for TSH (61% were novel), and notable findings for FT4 and T3, indicating that specific genes influence thyroid hormone levels and metabolism.
- The research findings enhance the understanding of thyroid hormone roles and suggest that variations in thyroid function may impact various health conditions including cardiovascular issues, autoimmune diseases, and cancer.
Article Synopsis
- Abdominal aortic aneurysm (AAA) has a significant genetic component, with a study identifying 141 genetic associations, including 97 that were previously unknown.
- The research highlighted key biological pathways related to AAA, such as lipid metabolism, vascular development, and inflammation, indicating how these factors contribute to the disease's progression.
- The study also suggests that lowering non-high-density lipoprotein cholesterol could be beneficial for AAA patients, advocating for the use of PCSK9 inhibitors based on evidence from a mouse model where PCSK9 loss prevented AAA development.
Article Synopsis
- A healthy placenta is crucial for both the mother and fetus during pregnancy, and this study uses placental weight as a measure of its growth.
- Genome-wide analyses across the genomes of mothers, fathers, and fetuses identified 40 genetic signals related to placental weight, revealing a mix of influences from both parents and the fetus.
- The findings suggest that higher placental weight, driven by fetal genetics, is linked to an increased risk of preeclampsia and shorter pregnancy duration, highlighting the role of fetal insulin in regulating placental growth.
Stroke is the second leading cause of death and disability worldwide. Stroke prevalence varies by sex and ancestry, possibly due to genetic heterogeneity between subgroups. We performed a genome-wide meta-analysis of 16 biobanks across multiple ancestries to study the genetics of ischemic stroke (60,176 cases, 1,310,725 controls) as part of the Global Biobank Meta-analysis Initiative (GBMI) and further combined the results with previously published MegaStroke.
View Article and Find Full Text PDFWhole genome sequencing has enabled new insights into the genetic architecture of complex traits, especially through access to low-frequency and rare variation. This highlights the key contributions from this technology and discusses considerations for its use and future perspectives.
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- A genome-wide association study (GWAS) was conducted on thoracic aortic aneurysms and dissections (TAAD) involving nearly 450,000 participants, identifying 21 genetic risk loci, 17 of which are new findings.
- The study utilized various analytical methods to pinpoint specific genes and cell types linked to TAAD, reinforcing that it is a unique condition not caused by the usual vascular disease factors.
- The research highlights that the genetic basis of TAAD is complex, similar to other traits, and is not only influenced by significant protein-altering gene variants.
Article Synopsis
- A major study involving 580,869 participants identified 1,020 genetic signals linked to lung function impairment, which is crucial in understanding chronic obstructive pulmonary disease (COPD) and predicting mortality.
- * The research found 559 genes related to lung function that were connected to 29 different biological pathways and demonstrated variations across ancestry, age, and smoking habits.
- * Findings suggest potential new targets for therapy by highlighting specific genetic variants and proteins, ultimately contributing to better understanding and treatment of COPD.
Biobanks of linked clinical patient histories and biological samples are an efficient strategy to generate large cohorts for modern genetics research. Biobank recruitment varies by factors such as geographic catchment and sampling strategy, which affect biobank demographics and research utility. Here, we describe the Michigan Genomics Initiative (MGI), a single-health-system biobank currently consisting of >91,000 participants recruited primarily during surgical encounters at Michigan Medicine.
View Article and Find Full Text PDFThe Trøndelag Health Study (HUNT) is a population-based cohort of ∼229,000 individuals recruited in four waves beginning in 1984 in Trøndelag County, Norway. Approximately 88,000 of these individuals have available genetic data from array genotyping. HUNT participants were recruited during four community-based recruitment waves and provided information on health-related behaviors, self-reported diagnoses, family history of disease, and underwent physical examinations.
View Article and Find Full Text PDFBiobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.
View Article and Find Full Text PDFPolygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies have thoroughly investigated their best practices in global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance in 9 different biobanks for 14 disease endpoints.
View Article and Find Full Text PDFLinkage analysis, a class of methods for detecting co-segregation of genomic segments and traits in families, was used to map disease-causing genes for decades before genotyping arrays and dense SNP genotyping enabled genome-wide association studies in population samples. Population samples often contain related individuals, but the segregation of alleles within families is rarely used because traditional linkage methods are computationally inefficient for larger datasets. Here, we describe Population Linkage, a novel application of Haseman-Elston regression as a method of moments estimator of variance components and their standard errors.
View Article and Find Full Text PDFImportance: Protein-truncating variants (PTVs) in apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with significantly lower low-density lipoprotein (LDL) cholesterol concentrations. The association of these PTVs with coronary heart disease (CHD) warrants further characterization in large, multiracial prospective cohort studies.
Objective: To evaluate the association of PTVs in APOB and PCSK9 with LDL cholesterol concentrations and CHD risk.
Background: The 10-year Atherosclerotic Cardiovascular Disease risk score is the standard approach to predict risk of incident cardiovascular events, and recently, addition of coronary artery disease (CAD) polygenic scores has been evaluated. Although age and sex strongly predict the risk of CAD, their interaction with genetic risk prediction has not been systematically examined. This study performed an extensive evaluation of age and sex effects in genetic CAD risk prediction.
View Article and Find Full Text PDFBackground: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.
Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.
Article Synopsis
- MetaSTAAR is a new framework designed for analyzing rare genetic variants in large studies, specifically whole genome and whole exome sequencing (WGS/WES).
- It effectively manages relatedness and population differences while analyzing various traits, enhancing the ability to detect significant rare variant associations by utilizing functional annotations.
- In tests with over 30,000 diverse samples, MetaSTAAR yielded results similar to pooled data analysis and successfully identified significant rare variant associations related to lipid traits.
Article Synopsis
- - The study investigates how a specific large noncoding genomic segment linked to bicuspid aortic valve (BAV) affects the endothelial-mesenchymal transition (EndoMT), a crucial process in heart valve formation.
- - Researchers used CRISPR technology to delete this genomic segment in induced pluripotent stem cells (hiPSCs), finding that this deletion impaired EndoMT and reduced the expression of key genes involved in this process.
- - Single-cell RNA sequencing revealed important insights into the molecular mechanisms at play, highlighting potential regulatory roles of genes such as TWIST1, particularly in cells derived from BAV patients.
Article Synopsis
- Tobacco and alcohol use contribute significantly to global mortality rates, with heritability playing a key role in these behaviors.
- This study utilized genetic data from a diverse population of 3.4 million individuals, including 21% non-European ancestry, to identify genetic variants linked to tobacco and alcohol use.
- Findings showed that while increased genetic diversity improved the identification of genomic loci, polygenic risk scores were less effective across different ancestries, underscoring the need for larger and more diverse genetic datasets for better predictive outcomes.