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doi:10.1177/0956797611420301 pmid:21960248 pmcid:PMC3212636 fatcat:w3fv3khhh5axlcpeiqjjgg6hii
ABSTRACTObjectiveGenetic screening is the gold standard for biogeographical ancestry (i.e. race), but this information is often unavailable to those developing research studies. We assessed agreement between census- and electronic health record (EHR)-derived demographic data with genetic ancestry to determine if these sources could support selection of diverse cohorts.Materials and MethodsWe identified a population of 4,837 genotyped patients and determined concordance between genetic measuresdoi:10.1101/598706 fatcat:3g5ryfjlobgq3as57ompttqj5e
more »... f ancestry against race derived from decennial nationwide census, electronic medical records, and self-report.ResultsWe identified a 90% or greater concordance between the EHR-derived data and genetic ancestry. Census data had a high concordance (97%) with genetic and self-reported data for patients of European ancestry but low concordance for patients of African ancestry (64%).Discussion and ConclusionsThe high concordance between EHR-derived race and genetic ancestry suggests that EHR-derived information could be an effective proxy for race when recruiting for diverse research cohorts.
Background-Cross-sectional studies of the association between hypertension (HTN) and brain atrophy have shown reductions in prefrontal, temporal, and hippocampal volumes, and have identified thinner cortices across the cortical mantle. Method-In the current study, we followed 96 participants enrolled in the Baltimore Longitudinal Study of Aging over a mean interval of 8 years (mean age at baseline = 68.7) and compared those who are hypertensive (n = 49) throughout the study with those who aredoi:10.1097/hjh.0000000000000531 pmid:25693060 pmcid:PMC5912213 fatcat:af5ctlr6rnc5ppb62juhsyimwm
more »... rmotensive (n = 47). Results-Hypertensive individuals show an increased rate of thinning compared with normotensive individuals in several regions, including the frontomarginal gyrus in the left hemisphere, and the superior temporal, fusiform, and lateral orbitofrontal cortex in the right hemisphere. We also investigated the effects of midlife blood pressure (BP), intervisit variability in BP prior to imaging, and duration of HTN on areas that show subsequent differences in the rates of cortical thinning between groups. We found that higher midlife BP and longer durations of HTN predicted a higher rate of thinning in the right superior temporal gyrus. We also found that greater variability in SBP but not DBP predicted a higher rate of thinning in the right superior temporal gyrus, frontomarginal gyrus, and occipital pole. Conclusion-These findings demonstrate that hypertensive individuals show increased rates of thinning compared with normotensive individuals and suggest intervisit BP variability and midlife BP contribute to these longitudinal differences.
a i;ℓ m tÀ1 i;ℓ 1 f 2 þ jjδ t ð Þ i jj 2 2 2 ¼ 0; ð8Þ δ t ð Þ i ¼ y t ð Þ i À x t ð Þ i ; ℓ ¼ 1; …; d; where y ðtÞ i;l and a i;l denote the l th component of y i (t) and a i , respectively, l ¼ 1; …; ... Under the diagonal assumption of M i , the update equations are as follows, ∑ T t¼1 t À 1 ð Þ y t ð Þ i;ℓ À m tÀ1 i;ℓ a i;ℓ m t i;ℓ 1 f 2 þ jjδ t ð Þ i jj 2 2 2 ¼ 0; ð7Þ ∑ T t¼1 y t ð Þ i;ℓ À m tÀ1 i;ℓ ...doi:10.1016/j.nicl.2016.02.005 pmid:26958465 pmcid:PMC4773508 fatcat:rte33fsizbcefnrw3zidf525li
g Hg/L, resp.). ... The reference lines at 0.956 g/L and 1.14 g/L indicate the 95% CI for THg in the US population from NHANES  . predictors are summarized in Table 2 . ... Authors' Contribution Jennifer Ong and Esther Erdei contributed equally to this work. ...doi:10.1155/2014/325461 pmid:24864198 pmcid:PMC4017878 fatcat:yfllokisbfdf5k6phjwfe7du4i
At level (L), entorhinal islands are no longer observed. ... A coordinate system is labeled, 'd' for dorsal, 'v' for ventral, 'l' for lateral and 'm' for medial in A for all panels. ...doi:10.1016/j.neuroimage.2009.04.033 pmid:19376238 pmcid:PMC2738987 fatcat:idjzay6c2faw7jwxecylko3wju
Perturbations in the prefrontal cortex (PFC), hippocampus, and amygdala are implicated in the development of anxiety disorders. However, most structural neuroimaging studies of patients with anxiety disorders utilize adult samples, and the few studies in youths examine small samples, primarily with volume-based measures. This study tested the hypothesis that cortical thickness of PFC regions and gray matter volume of the hippocampus and amygdala differ between pediatric anxiety disorderdoi:10.1038/npp.2017.83 pmid:28436445 fatcat:gyu2owgl3jawzlrsksnfmllkky
more »... and healthy volunteers (HVs). High-resolution 3-Tesla T1-weighted MRI scans were acquired in 151 youths (75 anxious, 76 HV; ages 8-18). Analyses tested associations of brain structure with anxiety diagnosis and severity across both groups, as well as response to cognitive-behavioral therapy in a subset of 53 patients. Cortical thickness was evaluated both within an a priori PFC mask (small-volume corrected) and using an exploratory whole-brain-corrected (po0.05) approach. Anxious relative to healthy youths exhibited thicker cortex in the left ventromedial PFC (vmPFC) and left precentral gyrus. Both anxiety diagnosis and symptom severity were associated with smaller right hippocampal volume. In patients, thinner cortex in parietal and occipital cortical regions was associated with worse treatment response. Pediatric anxiety was associated with structural differences in vmPFC and hippocampus, regions implicated in emotional processing and in developmental models of anxiety pathophysiology. Parietal and occipital cortical thickness were related to anxiety treatment response but not baseline anxiety.
Age-related macular degeneration (AMD), a multifactorial, neurodegenerative disease, is a leading cause of vision loss. With the rapid advancement of DNA sequencing technologies, many AMDassociated genetic polymorphisms have been identified. Currently, the most time consuming steps of these studies are patient recruitment and phenotyping. In this study, we describe the development of an automated algorithm to identify neovascular (wet) AMD, non-neovascular (dry) AMD and control subjects usingdoi:10.1038/srep12875 pmid:26255974 pmcid:PMC4530462 fatcat:t7nu5wlrwvezdetaefbm326z6u
more »... ectronic medical record (EMR)-based criteria. Positive predictive value (91.7%) and negative predictive value (97.5%) were calculated using expert chart review as the gold standard to assess algorithm performance. We applied the algorithm to an EMR-linked DNA bio-repository to study previously identified AMD-associated single nucleotide polymorphisms (SNPs), using case/ control status determined by the algorithm. Risk alleles of three SNPs, rs1061170 (CFH), rs1410996 (CFH), and rs10490924 (ARMS2) were found to be significantly associated with the AMD case/control status as defined by the algorithm. With the rapid growth of EMR-linked DNA biorepositories, patient selection algorithms can greatly increase the efficiency of genetic association study. We have found that stepwise validation of such an algorithm can result in reliable cohort selection and, when coupled within an EMR-linked DNA biorepository, replicates previously published AMD-associated SNPs. Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disease that is the leading cause of blindness in western individuals over the age of 65 1-4 . Clinical presentation of AMD is heterogeneous, with many genetic and environmental risk factors contributing to its pathogenesis 5 . The rate of identification of AMD-associated genetic risk factors, including but not limited to single nucleotide polymorphisms (SNPs) in CFH, ARMS2 and HTRA1 genes, has increased rapidly with the utilization of genome-wide association studies (GWAS) 6-9 . These studies have led to a better understanding of AMD pathophysiology, creation of genetic based prediction models and a plethora of AMD pharmacogenomics studies 8,10-15 . GWAS studies have also identified environmental exposures that interact with AMD genetic risk factors, highlighting the importance of developing accurate criteria for clinical phenotyping in order to discriminate disease and control populations 16,17 . One important barrier to genetic association
Dellefave L, McNally EM. The genetics of dilated cardiomyopathy. Current opinion in cardiology. 2010;25(3):198-204. 36. Ghosh R, Oak N, Plon SE. ...doi:10.1101/716662 fatcat:5gfjs4ss4renjbvrsihhy6ki6q
This boundary is selected from an ℓ,b map of a velocity slice ±5 km s −1 about the cloud's systemic velocity as given by HRK88. ...arXiv:astro-ph/9811291v1 fatcat:vloyiqocfbgmnba2e7gsx3xree
A fundamental question in development is how cells assemble to form a tubular network during organ formation. In glandular organs, tubulogenesis is a multistep process requiring coordinated proliferation, polarization and reorganization of epithelial cells to form a lumen, and lumen expansion. Although it is clear that epithelial cells possess an intrinsic ability to organize into polarized structures, the mechanisms coordinating morphogenetic processes during tubulogenesis are poorlydoi:10.1016/j.devcel.2014.06.012 pmid:25158854 pmcid:PMC4155578 fatcat:cw6fsvofqveejegxl7n4i3tlfa
more »... . Here, we demonstrate that parasympathetic nerves regulate tubulogenesis in the developing salivary gland. We show that vasoactive intestinal peptide (VIP) secreted by the innervating ganglia promotes ductal growth, leads to the formation of a contiguous lumen, and facilitates lumen expansion through a cyclic AMP/ protein kinase A (cAMP/PKA)-dependent pathway. Furthermore, we provide evidence that lumen expansion is independent of apoptosis and involves the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-regulated Cl(À) channel. Thus, parasympathetic innervation coordinates multiple steps in tubulogenesis during organogenesis.
L. C.), or a supervised neuropsychology trainee, administered all neuropsychological tests. ...doi:10.1682/jrrd.2013.11.0246 pmid:25625824 fatcat:4s5hwpjlxre5vo3myds2qeft2e
and objective: There is an increasing desire to share de-identified electronic health records (EHRs) for secondary uses, but there are concerns that clinical terms can be exploited to compromise patient identities. Anonymization algorithms mitigate such threats while enabling novel discoveries, but their evaluation has been limited to single institutions. Here, we study how an existing clinical profile anonymization fares at multiple medical centers. Methods: We apply a state-of-the-artdoi:10.1093/jamia/ocv154 pmid:26567325 pmcid:PMC4954623 fatcat:djpbiqedqjesjdfrie6xqwf7ai
more »... ization algorithm, with k set to the standard value 5, to the International Classification of Disease, ninth edition codes for patients in a hypothyroidism association study at three medical centers: Marshfield Clinic, Northwestern University, and Vanderbilt University. We assess utility when anonymizing at three population levels: all patients in 1) the EHR system; 2) the biorepository; and 3) a hypothyroidism study. We evaluate utility using 1) changes to the number included in the dataset, 2) number of codes included, and 3) regions generalization and suppression were required. Results: Our findings yield several notable results. First, we show that anonymizing in the context of the entire EHR yields a significantly greater quantity of data by reducing the amount of generalized regions from $15% to $0.5%. Second, $70% of codes that needed generalization only generalized two or three codes in the largest anonymization. Conclusions: Sharing large volumes of clinical data in support of phenome-wide association studies is possible while safeguarding privacy to the underlying individuals.
ABSTRACTApproximately 6 million adults in the US have heart failure (HF). HF progression is variable due in part to differences in sex, age, and genetic ancestry. Previous population-based genetic studies have largely focused on cross-sectional data related to HF, a disease known to change over time. Utilizing longitudinal data trajectory probabilities as a continuous trait may increase the likelihood of finding significant, biologically relevant associations in a genome-wide association (GWA)doi:10.1101/2020.05.10.087130 fatcat:uryirpeyfzbgbp2psd2icgltse
more »... nalysis. We analyzed data from the electronic health record in a medical biobank from a single, metropolitan US center to gather clinically pertinent data for analyses. We evaluated whole genome sequencing of 896 unrelated biobank participants, including 494 with at least 1 electrocardiogram and 324 who had more than 1 echocardiogram (∼3 observations per person). A censored normal distribution multivariable mixture model was used to cluster phenotype measures for genome-wide analyses. GWA analysis on the trajectory probability of the corrected QT measurement (QTc) taken from electrocardiograms identified significant associations with variants in regulatory regions proximal to the WLS gene, which encodes the Wnt ligand secretion mediator, Wntless. WLS was previously associated with QT length using of approximately 16,000 participants supporting the utility of this method to uncover significant genetic associations in small datasets. GWA analysis on the trajectory probability of left ventricular diameter as taken from echocardiograms identified novel significant associations with variants in regulatory regions near MYO10, which encodes the unconventional Myosin-10. We found that trajectory probabilities improved the ability to discover significant and relevant genetic associations. This novel approach increased yield from smaller, well-phenotyped cohorts with longitudinal data from a medical biobank.AUTHOR SUMMARYApproximately 6 million adults in the US have heart failure, a disease known to change over time. In a hospital based electronic health record, electrocardiograms and echocardiograms, used to evaluate heart failure, can be tracked over time. We utilized these data to create a novel trait that can be applied to genetic analyses. We analyzed genome sequence of 896 biobank participants from diverse racial/ethnic backgrounds. Genome-wide association (GWA) analyses were performed on a subset of these individuals for heart failure outcomes. A statistical model that incorporates cardiac data that are tracked over time was used to cluster these data using a probabilistic approach. These probabilities were used for a GWA analysis for corrected QT measurement (QTc) and left ventricular diameter (LVID). The QTc interval analysis identified significant correlations with variants in regulatory regions near the WLS gene which encodes the Wnt ligand secretion mediator, Wntless. Analysis of LVID identified significant associations with variants in regulatory regions near the MYO10 gene which encodes the unconventional Myosin-10. Through these analyses, we found that using the trajectory probabilities can facilitate the discovery of novel significant, biologically relevant associations. This method reduces the need for larger cohorts, and increases yield from smaller, well-phenotyped cohorts.
The racial and ethnic distribution is consistent with the patient MEDINFO 2019: Health and Wellbeing e-Networks for All L. Ohno-Machado and B. ...doi:10.3233/shti190487 pmid:31438184 fatcat:n7usv2lok5a37ihi6ku4psm47m
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