Web–Enabled Classification of SNPs for Genome–Wide Association Studies

2008 ◽  
Author(s):  
Abhijit R. Tendulkar ◽  
Nikola Stojanovic ◽  
Robert Barber
Keyword(s):  
Association Studies

Seronegative Spondyloarthritis: Epidemiology, Pathogenesis, And Pathology

2018 ◽  
Author(s):  
Walter P Maksymowych
Keyword(s):  
Association Studies ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Population Based ◽  
Cell Phenotype ◽  
Imaging Data ◽  
Leukocyte Antigen ◽  
Seronegative Spondyloarthritis ◽  
Magnetic Resonance Imaging Mri

Classification of spondyloarthritis (SpA) is aimed at including patients with radiographic evidence of sacroiliitis and those with early disease who do not yet meet radiographic criteria but have positive features on magnetic resonance imaging (MRI). Most studies report a prevalence of SpA of 0.1 to 0.6%. Human leukocyte antigen (HLA)-B27 contributes approximately 20% of the heritability of SpA, and non–major histocompatibility complex loci identified to date (n = 113) contribute another approximately 10%. To date, 160 subtypes of HLA-B*27 have been reported, although population-based disease association studies are limited to only a few subtypes. Subtypes HLA-B*27:05 and HLA-B*27:04 are examples of subtypes associated with disease, whereas HLA-B*27:06 and HLA-B*27:09 are nonassociated. Properties of the B27 molecule relevant to pathogenesis include antigen presentation, propensity to misfold, and formation of homodimers. Key pathways identified by genetic studies include the interleukin (IL)-23 and M1-aminopeptidase pathways. The latter pathway is involved in peptide trimming in the endoplasmic reticulum, changing both the length and amino acid composition of peptides available for HLA class I presentation. IL-23 is a key cytokine regulating expression of IL-17 in a specific T helper cell phenotype, Th17, and also a variety of cells of the innate immune system. The IL-23–IL-17 pathway has been directly implicated in inflammation at sites that are inflamed in SpA. Increasing evidence based on prospective clinical and imaging data supports a link between inflammation and ankylosis, especially if the resolution of inflammation is followed by the appearance of a particular type of reparative tissue, namely, fat metaplasia, on T1-weighted MRI. This review contains 8 figures, 5 tables and 33 references Key words: association, classification, genetics, heritability, innate immunity, prevalence, spondyloarthritis

scholarly journals Developing and Evaluating Mappings of ICD-10 and ICD-10-CM Codes to PheCodes

2018 ◽  
Author(s):  
Patrick Wu ◽  
Aliya Gifford ◽  
Xiangrui Meng ◽  
Xue Li ◽  
Harry Campbell ◽  
...  
Keyword(s):  
Medical Center ◽  
Association Studies ◽  
International Classification Of Diseases ◽  
Snomed Ct ◽  
Unified Medical Language System ◽  
Classification Of Diseases ◽  
Icd 10 ◽  
The Uk ◽  
Systematized Nomenclature Of Medicine

AbstractBackgroundThe PheCode system was built upon the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) for phenome-wide association studies (PheWAS) in the electronic health record (EHR).ObjectiveHere, we present our work on the development and evaluation of maps from ICD-10 and ICD-10-CM codes to PheCodes.MethodsWe mapped ICD-10 and ICD-10-CM codes to PheCodes using a number of methods and resources, such as concept relationships and explicit mappings from the Unified Medical Language System (UMLS), Observational Health Data Sciences and Informatics (OHDSI), Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT), and National Library of Medicine (NLM). We assessed the coverage of the maps in two databases: Vanderbilt University Medical Center (VUMC) using ICD-10-CM and the UK Biobank (UKBB) using ICD-10. We assessed the fidelity of the ICD-10-CM map in comparison to the gold-standard ICD-9-CM→PheCode map by investigating phenotype reproducibility and conducting a PheWAS.ResultsWe mapped >75% of ICD-10-CM and ICD-10 codes to PheCodes. Of the unique codes observed in the VUMC (ICD-10-CM) and UKBB (ICD-10) cohorts, >90% were mapped to PheCodes. We observed 70-75% reproducibility for chronic diseases and <10% for an acute disease. A PheWAS with a lipoprotein(a) (LPA) genetic variant, rs10455872, using the ICD-9-CM and ICD-10-CM maps replicated two genotype-phenotype associations with similar effect sizes: coronary atherosclerosis (ICD-9-CM: P < .001, OR = 1.60 vs. ICD-10-CM: P < .001, OR = 1.60) and with chronic ischemic heart disease (ICD-9-CM: P < .001, OR = 1.5 vs. ICD-10-CM: P < .001, OR = 1.47).ConclusionsThis study introduces the initial “beta” versions of ICD-10 and ICD-10-CM to PheCode maps that will enable researchers to leverage accumulated ICD-10 and ICD-10-CM data for high-throughput PheWAS in the EHR.

Form prominence in the L2 lexicon: Further evidence from word association

2019 ◽  
Vol 37 (1) ◽  
pp. 69-90
Author(s):  
Nan Jiang ◽  
Jianqin Zhang
Keyword(s):  
Native Speakers ◽  
Word Association ◽  
Native Speaker ◽  
Association Studies ◽  
First Language ◽  
The Past ◽  
Definition Of ◽  
Orthographic Priming ◽  
Selection Of

Two lines of evidence emerged in the past suggesting that lexical form seemed to play a more important role in the organization of the second language (L2) mental lexicon than in that of the first language (L1) lexicon. They were masked orthographic priming in L2 word recognition and an elevated proportion of form-related responses in L2 word association. However, findings from previous word association studies were inconsistent regarding (1) how often L2 speakers produced form-related responses ( flood–blood) and (2) whether L2 speakers were more likely than L1 speakers to provide such responses. Attributing this inconsistency to two methodological causes, the classification of form-related responses and the selection of stimuli, the present study adopted an improved approach by quantifying the definition of form-related responses and by selecting stimuli that had both strong semantic associates and orthographically similar words as potential responses. The latter improvement helped remove the bias for producing either meaning-based or form-based responses. A group of 30 English native speakers and two groups of 65 non-native speakers were tested on the same set of stimuli of 74 English words. Three findings were obtained: (1) non-native speakers produced significantly more form-related responses than native speakers, (2) the two non-native speaker group who differed in L2 experiences showed comparable results, and (3) the participants’ familiarity with the stimuli and the lexical frequency of the stimuli negatively correlated with the proportion of form-related responses among non-native speakers. These results provided more compelling evidence for form prominence in the L2 lexicon.

scholarly journals Mapping ICD-10 and ICD-10-CM Codes to Phecodes: Workflow Development and Initial Evaluation

10.2196/14325 ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. e14325 ◽  
Author(s):  
Patrick Wu ◽  
Aliya Gifford ◽  
Xiangrui Meng ◽  
Xue Li ◽  
Harry Campbell ◽  
...  
Keyword(s):  
Medical Center ◽  
Association Studies ◽  
International Classification Of Diseases ◽  
International Classification ◽  
Initial Evaluation ◽  
Unified Medical Language System ◽  
Classification Of Diseases ◽  
Icd 10 ◽  
The Uk

Background The phecode system was built upon the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) for phenome-wide association studies (PheWAS) using the electronic health record (EHR). Objective The goal of this paper was to develop and perform an initial evaluation of maps from the International Classification of Diseases, 10th Revision (ICD-10) and the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes to phecodes. Methods We mapped ICD-10 and ICD-10-CM codes to phecodes using a number of methods and resources, such as concept relationships and explicit mappings from the Centers for Medicare & Medicaid Services, the Unified Medical Language System, Observational Health Data Sciences and Informatics, Systematized Nomenclature of Medicine-Clinical Terms, and the National Library of Medicine. We assessed the coverage of the maps in two databases: Vanderbilt University Medical Center (VUMC) using ICD-10-CM and the UK Biobank (UKBB) using ICD-10. We assessed the fidelity of the ICD-10-CM map in comparison to the gold-standard ICD-9-CM phecode map by investigating phenotype reproducibility and conducting a PheWAS. Results We mapped >75% of ICD-10 and ICD-10-CM codes to phecodes. Of the unique codes observed in the UKBB (ICD-10) and VUMC (ICD-10-CM) cohorts, >90% were mapped to phecodes. We observed 70-75% reproducibility for chronic diseases and <10% for an acute disease for phenotypes sourced from the ICD-10-CM phecode map. Using the ICD-9-CM and ICD-10-CM maps, we conducted a PheWAS with a Lipoprotein(a) genetic variant, rs10455872, which replicated two known genotype-phenotype associations with similar effect sizes: coronary atherosclerosis (ICD-9-CM: P<.001; odds ratio (OR) 1.60 [95% CI 1.43-1.80] vs ICD-10-CM: P<.001; OR 1.60 [95% CI 1.43-1.80]) and chronic ischemic heart disease (ICD-9-CM: P<.001; OR 1.56 [95% CI 1.35-1.79] vs ICD-10-CM: P<.001; OR 1.47 [95% CI 1.22-1.77]). Conclusions This study introduces the beta versions of ICD-10 and ICD-10-CM to phecode maps that enable researchers to leverage accumulated ICD-10 and ICD-10-CM data for PheWAS in the EHR.

scholarly journals Epigenome Wide Associations of Smoking Behavior in the Health and Retirement Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 668-668
Author(s):  
Jonah Fisher ◽  
Helen Meier ◽  
Jessica Faul ◽  
Colter Mitchell ◽  
Eileen Crimmins ◽  
...  
Keyword(s):  
Association Studies ◽  
Venous Blood ◽  
Smoking Behavior ◽  
Confounding Variables ◽  
Smoking Behaviors ◽  
Smoking Duration ◽  
The Common ◽  
Never Smokers ◽  
Linear Regressions

Abstract DNA methylation (DNAm) is an increasingly popular biomarker of health and aging outcomes. Smoking behaviors have a significant and well documented correlation with methylation signatures within the epigenome and are important confounding variables to account for in epigenome-wide association studies (EWAS). However, the common classification of individuals as ‘current’, ‘former’, and ‘never’ smokers may miss crucial DNAm patterns associated with other smoking behaviors such as duration, intensity, and frequency of cigarette smoking, resulting in an underestimation of the contribution of smoking behaviors to DNAm and potentially biasing EWAS results. We investigated associations between multiple smoking behavioral phenotypes (smoking pack years, smoking duration, smoking start age, and smoking end age) and single site DNAm using linear regressions adjusting for age, sex, race/ethnicity, education, and cell-type proportions in a subsample of individuals who participated in the HRS 2016 Venous Blood Study (N=1,775). DNAm was measured using the Infinium Methylation EPIC BeadChip. All 4 phenotypes had significant associations (FDR &lt; 0.05) with many methylation sites (packyears=6859, smoking duration=6572, start age=11374, quit age=773). There was not much overlap in DNAm sites between the full set of models with only 6 overlapping between all 4. However, the phenotypes packyears and smoking duration showed large overlap (N=3782). Results suggest additional smoking phenotypes beyond current/former/never smoker classification should be included in EWAS analyses to appropriately account for the influence of smoking behaviors on DNAm.

Vasculitis: Decade in Review

2018 ◽  
Vol 15 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Selcan Demir ◽  
Hafize Emine Sönmez ◽  
Seza Özen
Keyword(s):  
Targeted Therapies ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genetic Studies ◽  
The Past ◽  
Genome Wide ◽  
New Perspective

Background: In the last decade, we have come to better understand and manage the vasculitides. The classification of vasculitides has been revised. Genome- wide association studies and linkage analyses have been undertaken in hope of better understanding the pathogenesis of vasculitides. Comprehensive genetic studies have highlighted new pathways that may guide us in more targeted therapies. Description of the monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2), Haploinsufficiency of A20 (HA20), have introduced a new perspective to vasculopathies, and introduced alternative treatments for these diseases. Conclusion: In this review, the important discoveries in pathogenesis and consensus treatment recommendations from the past decade will be summarized.

scholarly journals The Genetics of Sleep Disorders in Children: A Narrative Review

2021 ◽  
Vol 11 (10) ◽  
pp. 1259
Author(s):  
Greta Mainieri ◽  
Angelica Montini ◽  
Antonio Nicotera ◽  
Gabriella Di Rosa ◽  
Federica Provini ◽  
...  
Keyword(s):  
Sleep Disorders ◽  
Association Studies ◽  
Single Gene ◽  
Brain Network ◽  
Narrative Review ◽  
Genome Wide Association Studies ◽  
Genetic Studies ◽  
Gene Environment ◽  
Genome Wide

Sleep is a universal, highly preserved process, essential for human and animal life, whose complete functions are yet to be unravelled. Familial recurrence is acknowledged for some sleep disorders, but definite data are lacking for many of them. Genetic studies on sleep disorders have progressed from twin and family studies to candidate gene approaches to culminate in genome-wide association studies (GWAS). Several works disclosed that sleep-wake characteristics, in addition to electroencephalographic (EEG) sleep patterns, have a certain degree of heritability. Notwithstanding, it is rare for sleep disorders to be attributed to single gene defects because of the complexity of the brain network/pathways involved. Besides, the advancing insights in epigenetic gene-environment interactions add further complexity to understanding the genetic control of sleep and its disorders. This narrative review explores the current genetic knowledge in sleep disorders in children, following the International Classification of Sleep Disorders—Third Edition (ICSD-3) categorisation.

Basic mechanisms, genetics, targets, and animal models for anxiety disorders

2020 ◽  
pp. 905-916
Author(s):  
Martien Kas ◽  
Berend Olivier
Keyword(s):  
Anxiety Disorders ◽  
Association Studies ◽  
Aminobutyric Acid ◽  
Genome Wide Association Studies ◽  
Gamma Aminobutyric Acid ◽  
Functional Studies ◽  
Diagnostic And Statistical Manual ◽  
Genome Wide ◽  
Preclinical And Clinical Studies

Historically, two extensively studied neurotransmitter systems have been studied in anxiety and anxiety disorders, namely the gamma-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT, serotonin) systems. Here, the chapter illuminates the various targets within these systems that have led to treatment or are potentially targets for the treatment of anxiety disorders. Human genome-wide association studies have offered potentially novel candidate genes for anxiety disorders, although replication often failed to confirm the original findings. A complicating factor is the heterogenous classification of anxiety disorders in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) and the complex translational operationalization of anxiety—preclinical and clinical studies use diverging definitions and models of anxiety. Stratification of patient populations based on quantitative biological parameters (rather than diagnosis), as well as functional studies in mice mutant for risk genes using homologous endpoints, might optimize our understanding of the relationships between risk genetic variations and core features of anxiety disorders.

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