Bioinformatics challenges in genome-wide association studies (GWAS).

Genome-wide association studies (GWAS) are a powerful tool for investigators to examine the human genome to detect genetic risk factors, reveal the genetic architecture of diseases and open up new opportunities for treatment and prevention. However, despite its successes, GWAS have not been able to identify genetic loci that are effective classifiers of disease, limiting […]

Investigating the relationship between mitochondrial genetic variation and cardiovascular-related traits to develop a framework for mitochondrial phenome-wide association studies.

Mitochondria play a critical role in the cell and have DNA independent of the nuclear genome. There is much evidence that mitochondrial DNA (mtDNA) variation plays a role in human health and disease, however, this area of investigation has lagged behind research into the role of nuclear genetic variation on complex traits and phenotypic outcomes. […]

Pleiotropic associations of risk variants identified for other cancers with lung cancer risk: the PAGE and TRICL consortia.

Genome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed.We included 18023 patients with lung […]

Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia.

Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal […]

Automated extraction of clinical traits of multiple sclerosis in electronic medical records.

The clinical course of multiple sclerosis (MS) is highly variable, and research data collection is costly and time consuming. We evaluated natural language processing techniques applied to electronic medical records (EMR) to identify MS patients and the key clinical traits of their disease course.We used four algorithms based on ICD-9 codes, text keywords, and medications […]

Utilization of an EMR-biorepository to identify the genetic predictors of calcineurin-inhibitor toxicity in heart transplant recipients.

Calcineurin-inhibitors CI are immunosuppressive agents prescribed to patients after solid organ transplant to prevent rejection. Although these drugs have been transformative for allograft survival, long-term use is complicated by side effects including nephrotoxicity. Given the narrow therapeutic index of CI, therapeutic drug monitoring is used to prevent acute rejection from underdosing and acute toxicity from […]

Associations between KCNJ6 (GIRK2) gene polymorphisms and pain-related phenotypes.

G-protein coupled inwardly rectifying potassium (GIRK) channels are effectors determining degree of analgesia experienced upon opioid receptor activation by endogenous and exogenous opioids. The impact of GIRK-related genetic variation on human pain responses has received little research attention. We used a tag single nucleotide polymorphism (SNP) approach to comprehensively examine pain-related effects of KCNJ3 (GIRK1) […]

The somatic genomic landscape of glioblastoma.

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase […]

Rapid storage and retrieval of genomic intervals from a relational database system using nested containment lists.

Efficient storage and retrieval of genomic annotations based on range intervals is necessary, given the amount of data produced by next-generation sequencing studies. The indexing strategies of relational database systems (such as MySQL) greatly inhibit their use in genomic annotation tasks. This has led to the development of stand-alone applications that are dependent on flat-file […]

Putting pleiotropy and selection into context defines a new paradigm for interpreting genetic data.

Natural selection shapes many human genes, including some related to complex diseases. Understanding how selection affects genes, especially pleiotropic ones, may be important in evaluating disease associations and the role played by environmental variation. This may be of particular interest for genes with antagonistic roles that cause divergent patterns of selection. The lectin-like low-density lipoprotein […]

ICD-9 tobacco use codes are effective identifiers of smoking status.

To evaluate the validity of, characterize the usage of, and propose potential research applications for International Classification of Diseases, Ninth Revision (ICD-9) tobacco codes in clinical populations.Using data on cancer cases and cancer-free controls from Vanderbilt’s biorepository, BioVU, we evaluated the utility of ICD-9 tobacco use codes to identify ever-smokers in general and high smoking […]