Showing papers by "David Reich published in 2012"
TL;DR: A suite of methods for learning about population mixtures are presented, implemented in a software package called ADMIXTOOLS, that support formal tests for whether mixture occurred and make it possible to infer proportions and dates of mixture.
Abstract: Population mixture is an important process in biology. We present a suite of methods for learning about population mixtures, implemented in a software package called ADMIXTOOLS, that support formal tests for whether mixture occurred and make it possible to infer proportions and dates of mixture. We also describe the development of a new single nucleotide polymorphism (SNP) array consisting of 629,433 sites with clearly documented ascertainment that was specifically designed for population genetic analyses and that we genotyped in 934 individuals from 53 diverse populations. To illustrate the methods, we give a number of examples that provide new insights about the history of human admixture. The most striking finding is a clear signal of admixture into northern Europe, with one ancestral population related to present-day Basques and Sardinians and the other related to present-day populations of northeast Asia and the Americas. This likely reflects a history of admixture between Neolithic migrants and the indigenous Mesolithic population of Europe, consistent with recent analyses of ancient bones from Sweden and the sequencing of the genome of the Tyrolean "Iceman."
1,877 citations
Max Planck Society1, Massachusetts Institute of Technology2, Harvard University3, University of California, Berkeley4, University of Washington5, Bilkent University6, Chinese Academy of Sciences7, University of California, Santa Cruz8, University of Arizona9, Russian Academy of Sciences10, Howard Hughes Medical Institute11
TL;DR: The genomic sequence provides evidence for very low rates of heterozygosity in the Denisova, probably not because of recent inbreeding, but instead because of a small population size, and illuminates the relationships between humans and archaics, including Neandertals, and establishes a catalog of genetic changes within the human lineage.
Abstract: We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30×) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of “missing evolution” in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.
1,690 citations
TL;DR: This work presents an approach in which 192 sequencing libraries can be produced in a single day of technician time at a cost of about $15 per sample, effective not only for low-pass whole-genome sequencing, but also for simultaneously enriching them in pools of approximately 100 individually barcoded samples for a subset of the genome.
Abstract: Improvements in technology have reduced the cost of DNA sequencing to the point that the limiting factor for many experiments is the time and reagent cost of sample preparation. We present an approach in which 192 sequencing libraries can be produced in a single day of technician time at a cost of about $15 per sample. These libraries are effective not only for low-pass whole-genome sequencing, but also for simultaneously enriching them in pools of approximately 100 individually barcoded samples for a subset of the genome without substantial loss in efficiency of target capture. We illustrate the power and effectiveness of this approach on about 2000 samples from a prostate cancer study.
924 citations
Harvard University1, Massachusetts Institute of Technology2, University College London3, University of Hong Kong4, Aix-Marseille University5, University of Geneva6, University of Antioquia7, National Scientific and Technical Research Council8, University of Buenos Aires9, Universidade Federal do Rio Grande do Sul10, Federal University of Paraná11, National Autonomous University of Mexico12, Mexican Social Security Institute13, Instituto Politécnico Nacional14, Nestlé15, Universidad Autónoma de Nuevo León16, University of Santiago de Compostela17, Cayetano Heredia University18, University of Chicago19, Russian Academy of Sciences20, Université de Montréal21, University of Costa Rica22, Swiss Institute of Bioinformatics23, University of Bern24, University of Tarapacá25, Paul Sabatier University26, University of California, Berkeley27, Yale University28, Semel Institute for Neuroscience and Human Behavior29
TL;DR: It is shown that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America.
Abstract: The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.
696 citations
University of Cambridge1, University of Bristol2, University of Eastern Finland3, University of Helsinki4, University of Gothenburg5, University of Lille Nord de France6, Laval University7, Harvard University8, University of Edinburgh9, University of Sheffield10, Stanford University11, Uppsala University12, University of Pennsylvania13, Karolinska Institutet14, Pierre-and-Marie-Curie University15, University of Birmingham16, University of Michigan17, Technische Universität München18, Utrecht University19, University of Amsterdam20, University of Iceland21, National Institute for Health and Welfare22, National Institutes of Health23, Imperial College London24, University of Copenhagen25, Copenhagen University Hospital26, Clinical Trial Service Unit27, National Institute for Health Research28, deCODE genetics29, University of Oxford30
TL;DR: In this article, a functional genetic variant known to affect IL6R signalling was studied to assess whether this pathway is causally relevant to coronary heart disease, and Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking.
Abstract: Background Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
628 citations
TL;DR: This article measured the extent of linkage disequilibrium (LD) in the genomes of present-day Europeans and found that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000-86,000 years before the present (BP), and most likely 47,000 -65000 years ago.
Abstract: Comparisons of DNA sequences between Neandertals and present-day humans have shown that Neandertals share more genetic variants with non-Africans than with Africans. This could be due to interbreeding between Neandertals and modern humans when the two groups met subsequent to the emergence of modern humans outside Africa. However, it could also be due to population structure that antedates the origin of Neandertal ancestors in Africa. We measure the extent of linkage disequilibrium (LD) in the genomes of present-day Europeans and find that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000–86,000 years before the present (BP), and most likely 47,000–65,000 years ago. This supports the recent interbreeding hypothesis and suggests that interbreeding may have occurred when modern humans carrying Upper Paleolithic technologies encountered Neandertals as they expanded out of Africa.
371 citations
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TL;DR: The extent of linkage disequilibrium (LD) in the genomes of present-day Europeans is measured and it is found that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000–86,000 years before the present (BP), and most likely 47,000-65,000 year ago.
Abstract: Comparisons of DNA sequences between Neandertals and present-day humans have shown that Neandertals share more genetic variants with non-Africans than with Africans. This could be due to interbreeding between Neandertals and modern humans when the two groups met subsequent to the emergence of modern humans outside Africa. However, it could also be due to population structure that antedates the origin of Neandertal ancestors in Africa. We measure the extent of linkage disequilibrium (LD) in the genomes of present-day Europeans and find that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000-86,000 years before the present (BP), and most likely 47,000-65,000 years ago. This supports the recent interbreeding hypothesis, and suggests that interbreeding may have occurred when modern humans carrying Upper Paleolithic technologies encountered Neandertals as they expanded out of Africa.
339 citations
TL;DR: By studying height, a classic polygenic trait, this work demonstrates the first human signature of widespread selection on standing variation, and shows that frequencies of alleles associated with increased height are systematically elevated in Northern Europeans compared with Southern Europeans.
Abstract: Strong signatures of positive selection at newly arising genetic variants are well documented in humans(1-8), but this form of selection may not be widespread in recent human evolution(9). Because many human traits are highly polygenic and partly determined by common, ancient genetic variation, an alternative model for rapid genetic adaptation has been proposed: weak selection acting on many pre-existing (standing) genetic variants, or polygenic adaptation(10-12). By studying height, a classic polygenic trait, we demonstrate the first human signature of widespread selection on standing variation. We show that frequencies of alleles associated with increased height, both at known loci and genome wide, are systematically elevated in Northern Europeans compared with Southern Europeans (P < 4.3 × 10(-4)). This pattern mirrors intra-European height differences and is not confounded by ancestry or other ascertainment biases. The systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients ∼10(-3)-10(-5) per allele) rather than genetic drift alone (P < 10(-15)).
337 citations
TL;DR: The largest study of new mutations to date, comprising 2,058 germline changes discovered by analyzing 85,289 Icelanders at 2,477 microsatellites, infer that the sequence mutation rate is 1.4–2.3 × 10−8 mutations per base pair per generation (90% credible interval) and that human-chimpanzee speciation occurred 3.7–6.6 million years ago.
Abstract: Mutations are the raw material of evolution but have been difficult to study directly. We report the largest study of new mutations to date, comprising 2,058 germline changes discovered by analyzing 85,289 Icelanders at 2,477 microsatellites. The paternal-to-maternal mutation rate ratio is 3.3, and the rate in fathers doubles from age 20 to 58, whereas there is no association with age in mothers. Longer microsatellite alleles are more mutagenic and tend to decrease in length, whereas the opposite is seen for shorter alleles. We use these empirical observations to build a model that we apply to individuals for whom we have both genome sequence and microsatellite data, allowing us to estimate key parameters of evolution without calibration to the fossil record. We infer that the sequence mutation rate is 1.4-2.3×10(-8) mutations per base pair per generation (90% credible interval) and that human-chimpanzee speciation occurred 3.7-6.6 million years ago.
320 citations
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TL;DR: A new weighted LD statistic is presented that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods and can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references.
Abstract: Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese.
313 citations
TL;DR: It is found that all individuals derive at least a few percent of their genomes from admixture with non-Khoisan populations that began ∼1,200 years ago, supporting the hypothesis of an ancient link between southern and eastern Africa.
Abstract: Southern and eastern African populations that speak non-Bantu languages with click consonants are known to harbour some of the most ancient genetic lineages in humans, but their relationships are poorly understood. Here, we report data from 23 populations analysed at over half a million single-nucleotide polymorphisms, using a genome-wide array designed for studying human history. The southern African Khoisan fall into two genetic groups, loosely corresponding to the northwestern and southeastern Kalahari, which we show separated within the last 30,000 years. We find that all individuals derive at least a few percent of their genomes from admixture with non-Khoisan populations that began ∼1,200 years ago. In addition, the East African Hadza and Sandawe derive a fraction of their ancestry from admixture with a population related to the Khoisan, supporting the hypothesis of an ancient link between southern and eastern Africa.
TL;DR: It is shown that extremely low-coverage sequencing captures almost as much of the common and low-frequency variation across the genome as SNP arrays, within the context of reductions in sample preparation and sequencing costs.
Abstract: Genome-wide association studies (GWAS) have proven to be a powerful method to identify common genetic variants contributing to susceptibility to common diseases. Here, we show that extremely low-coverage sequencing (0.1-0.5×) captures almost as much of the common (>5%) and low-frequency (1-5%) variation across the genome as SNP arrays. As an empirical demonstration, we show that genome-wide SNP genotypes can be inferred at a mean r(2) of 0.71 using off-target data (0.24× average coverage) in a whole-exome study of 909 samples. Using both simulated and real exome-sequencing data sets, we show that association statistics obtained using extremely low-coverage sequencing data attain similar P values at known associated variants as data from genotyping arrays, without an excess of false positives. Within the context of reductions in sample preparation and sequencing costs, funds invested in extremely low-coverage sequencing can yield several times the effective sample size of GWAS based on SNP array data and a commensurate increase in statistical power.
TL;DR: HAPI-UR (haplotype inference for unrelated samples), an algorithm that is designed to handle unrelated and/or trio and duo family data, that has accuracy comparable to or greater than existing methods, and that is computationally efficient and can be applied to 100,000 samples or more is presented.
Abstract: Haplotypes are an important resource for a large number of applications in human genetics, but computationally inferred haplotypes are subject to switch errors that decrease their utility. The accuracy of computationally inferred haplotypes increases with sample size, and although ever larger genotypic data sets are being generated, the fact that existing methods require substantial computational resources limits their applicability to data sets containing tens or hundreds of thousands of samples. Here, we present HAPI-UR (haplotype inference for unrelated samples), an algorithm that is designed to handle unrelated and/or trio and duo family data, that has accuracy comparable to or greater than existing methods, and that is computationally efficient and can be applied to 100,000 samples or more. We use HAPI-UR to phase a data set with 58,207 samples and show that it achieves practical runtime and that switch errors decrease with sample size even with the use of samples from multiple ethnicities. Using a data set with 16,353 samples, we compare HAPI-UR to Beagle, MaCH, IMPUTE2, and SHAPEIT and show that HAPI-UR runs 18× faster than all methods and has a lower switch-error rate than do other methods except for Beagle; with the use of consensus phasing, running HAPI-UR three times gives a slightly lower switch-error rate than Beagle does and is more than six times faster. We demonstrate results similar to those from Beagle on another data set with a higher marker density. Lastly, we show that HAPI-UR has better runtime scaling properties than does Beagle so that for larger data sets, HAPI-UR will be practical and will have an even larger runtime advantage. HAPI-UR is available online (see Web Resources).
TL;DR: Genetic ancestry has a significant association with type 2 diabetes above and beyond its association with non-genetic risk factors for type 1 diabetes in African Americans, but no single gene with a major effect is sufficient to explain a large portion of the observed population difference in risk of diabetes.
Abstract: The risk of type 2 diabetes is approximately 2-fold higher in African Americans than in European Americans even after adjusting for known environmental risk factors, including socioeconomic status (SES), suggesting that genetic factors may explain some of this population difference in disease risk. However, relatively few genetic studies have examined this hypothesis in a large sample of African Americans with and without diabetes. Therefore, we performed an admixture analysis using 2,189 ancestry-informative markers in 7,021 African Americans (2,373 with type 2 diabetes and 4,648 without) from the Atherosclerosis Risk in Communities Study, the Jackson Heart Study, and the Multiethnic Cohort to 1) determine the association of type 2 diabetes and its related quantitative traits with African ancestry controlling for measures of SES and 2) identify genetic loci for type 2 diabetes through a genome-wide admixture mapping scan. The median percentage of African ancestry of diabetic participants was slightly greater than that of non-diabetic participants (study-adjusted difference=1.6%, P,0.001). The odds ratio for diabetes comparing participants in the highest vs. lowest tertile of African ancestry was 1.33 (95% confidence interval 1.13–1.55), after adjustment for age, sex, study, body mass index (BMI), and SES. Admixture scans identified two potential loci for diabetes at 12p13.31 (LOD=4.0) and 13q14.3 (Z score=4.5, P=6.6610 26 ). In conclusion, genetic ancestry has a significant association with type 2 diabetes above and beyond its association with nongenetic risk factors for type 2 diabetes in African Americans, but no single gene with a major effect is sufficient to explain a large portion of the observed population difference in risk of diabetes. There undoubtedly is a complex interplay among specific genetic loci and non-genetic factors, which may both be associated with overall admixture, leading to the observed ethnic differences in diabetes risk.
TL;DR: Findings raise the hypothesis that hair relaxer use increases uterine leiomyomata risk, which is unrelated to age at first use or type of formulation.
Abstract: Hair relaxers are used by millions of black women, possibly exposing them to various chemicals through scalp lesions and burns. In the Black Women's Health Study, the authors assessed hair relaxer use in relation to uterine leiomyomata incidence. In 1997, participants reported on hair relaxer use (age at first use, frequency, duration, number of burns, and type of formulation). From 1997 to 2009, 23,580 premenopausal women were followed for incident uterine leiomyomata. Multivariable Cox regression was used to estimate incidence rate ratios and 95% confidence intervals. During 199,991 person-years, 7,146 cases of uterine leiomyomata were reported as confirmed by ultrasound (n = 4,630) or surgery (n = 2,516). The incidence rate ratio comparing ever with never use of relaxers was 1.17 (95% confidence interval (CI): 1.06, 1.30). Positive trends were observed for frequency of use (P(trend) < 0.001), duration of use (P(trend) = 0.015), and number of burns (P(trend) < 0.001). Among long-term users (≥10 years), the incidence rate ratios for frequency of use categories 3-4, 5-6, and ≥7 versus 1-2 times/year were 1.04 (95% CI: 0.92, 1.19), 1.12 (95% CI: 0.99, 1.27), and 1.15 (95% CI: 1.01, 1.31), respectively (P(trend) = 0.002). Risk was unrelated to age at first use or type of formulation. These findings raise the hypothesis that hair relaxer use increases uterine leiomyomata risk.
TL;DR: The admixture findings indicate that no single highly differentiated locus is responsible for the ethnic disparity in UL, raising the possibility that multiple variants jointly contribute to the higher incidence of UL in African Americans.
Abstract: Rates of uterine leiomyomata (UL) are 2-3 times higher in African Americans than in European Americans. It is unclear whether inherited factors explain the ethnic disparity. To investigate the presence of risk alleles for UL that are highly differentiated in frequency between African Americans and European Americans, the authors conducted an admixture-based genome-wide scan of 2,453 UL cases confirmed by ultrasound or surgery in the Black Women's Health Study (1997-2009), a national prospective cohort study. Controls (n = 2,102) were women who did not report a UL diagnosis through 2009. Mean percentage of European ancestry was significantly lower among cases (20.00%) than among controls (21.63%; age-adjusted mean difference = -1.76%, 95% confidence interval: -2.40, -1.12; P < 0.0001), and the association was stronger in younger cases. Admixture analyses showed suggestive evidence of association at chromosomes 2, 4, and 10. The authors also genotyped a dense set of tag single nucleotide polymorphisms at different loci associated with UL in Japanese women but failed to replicate the associations. This suggests that genetic variation for UL differs in populations with and without African ancestry. The admixture findings further indicate that no single highly differentiated locus is responsible for the ethnic disparity in UL, raising the possibility that multiple variants jointly contribute to the higher incidence of UL in African Americans.
TL;DR: Having genotyped 2,284 DNA samples from across the Indian subcontinent, it is found that the previously described west Eurasian -13910 C>T mutation accounts for nearly all the genetic variation the authors observed in the 400- to 700-bp LCT regulatory region that was sequenced.
Abstract: Milk consumption and lactose digestion after weaning are exclusively human traits made possible by the continued production of the enzyme lactase in adulthood. Multiple independent mutations in a 100-bp region—part of an enhancer—approximately 14-kb upstream of the LCT gene are associated with this trait in Europeans and pastoralists from Saudi Arabia and Africa. However, a single mutation of purported western Eurasian origin accounts for much of observed lactase persistence outside Africa. Given the high levels of present-day milk consumption in India, together with archaeological and genetic evidence for the independent domestication of cattle in the Indus valley roughly 7,000 years ago, we sought to determine whether lactase persistence has evolved independently in the subcontinent. Here, we present the results of the first comprehensive survey of the LCT enhancer region in south Asia. Having genotyped 2,284 DNA samples from across the Indian subcontinent, we find that the previously described west Eurasian -13910 C.T mutation accounts for nearly all the genetic variation we observed in the 400- to 700-bp LCT regulatory region that we sequenced. Geography is a significant predictor of -13910*T allele frequency, and consistent with other genomic loci, its distribution in India follows a general northwest to southeast declining pattern, although frequencies among certain neighboring populations vary substantially. We confirm that the mutation is identical by descent to the European allele and is associated with the same .1 Mb extended haplotype in both populations.
TL;DR: The “thrifty genotype” hypothesis proposes that the high prevalence of type 2 diabetes in Native Americans and admixed Latin Americans has a genetic basis and reflects an evolutionary adaptation to a past low calorie/high exercise lifestyle, but identification of the gene variants underpinning this hypothesis remains elusive.
Abstract: The “thrifty genotype” hypothesis proposes that the high prevalence of type 2 diabetes (T2D) in Native Americans and admixed Latin Americans has a genetic basis and reflects an evolutionary adaptation to a past low calorie/high exercise lifestyle. However, identification of the gene variants underpinning this hypothesis remains elusive. Here we assessed the role of Native American ancestry, socioeconomic status (SES) and 21 candidate gene loci in susceptibility to T2D in a sample of 876 T2D cases and 399 controls from Antioquia (Colombia). Although mean Native American ancestry is significantly higher in T2D cases than in controls (32% v 29%), this difference is confounded by the correlation of ancestry with SES, which is a stronger predictor of disease status. Nominally significant association (P 1 was observed for markers selected from previous T2D genome-wide association studies, consistent with a role for Old World variants in susceptibility to T2D in Latin Americans. No association was found to the only known Native American-specific gene variant previously associated with T2D in a Mexican sample (rs9282541 in ABCA1). An admixture mapping scan with 1,536 ancestry informative markers (AIMs) did not identify genome regions with significant deviation of ancestry in Antioquia. Exclusion analysis indicates that this scan rules out ∼95% of the genome as harboring loci with ancestry risk ratios >1.22 (at P < 0.05).
TL;DR: Overall, there was no independent association between non–record-keeping workstation use and hemodynamic variability or aberrancies during anesthesia either between cases or within cases.
Abstract: BACKGROUND Anesthesia information management system workstations in the anesthesia workspace that allow usage of non-record-keeping applications could lead to distraction from patient care. We evaluated whether non-record-keeping usage of the computer workstation was associated with hemodynamic variability and aberrancies. METHODS Auditing data were collected on eight anesthesia information management system workstations and linked to their corresponding electronic anesthesia records to identify which application was active at any given time during the case. For each case, the periods spent using the anesthesia information management system record-keeping module were separated from those spent using non-record-keeping applications. The variability of heart rate and blood pressure were also calculated, as were the incidence of hypotension, hypertension, and tachycardia. Analysis was performed to identify whether non-record-keeping activity was a significant predictor of these hemodynamic outcomes. RESULTS Data were analyzed for 1,061 cases performed by 171 clinicians. Median (interquartile range) non-record-keeping activity time was 14 (1, 38) min, representing 16 (3, 33)% of a median 80 (39, 143) min of procedure time. Variables associated with greater non-record-keeping activity included attending anesthesiologists working unassisted, longer case duration, lower American Society of Anesthesiologists status, and general anesthesia. Overall, there was no independent association between non-record-keeping workstation use and hemodynamic variability or aberrancies during anesthesia either between cases or within cases. CONCLUSION Anesthesia providers spent sizable portions of case time performing non-record-keeping applications on anesthesia information management system workstations. This use, however, was not independently associated with greater hemodynamic variability or aberrancies in patients during maintenance of general anesthesia for predominantly general surgical and gynecologic procedures.
TL;DR: Complex thoracic aortic repairs requiring prolonged selective cerebral perfusion were associated with decline in neurocognitive function, and multiple regression analyses revealed that selective cerebral perfume time was a significant predictor of decline in performance on memory and language tests.
TL;DR: The development of a standard terminology for anaesthesia is described and also a Domain Analysis Model and implementation guide to facilitate a standard representation of AIMS records as extensible markup language documents that are compliant with the Health Level 7 Version 3 clinical document architecture are described.
Abstract: With the increasing use of anaesthesia information management systems (AIMS) there is the opportunity for different institutions to aggregate and share information both nationally and internationally. Potential uses of such aggregated data include outcomes research, benchmarking and improvement in clinical practice and patient safety. However, these goals can only be achieved if data contained in records from different sources are truly comparable and there is semantic inter-operability. This paper describes the development of a standard terminology for anaesthesia and also a Domain Analysis Model and implementation guide to facilitate a standard representation of AIMS records as extensible markup language documents that are compliant with the Health Level 7 Version 3 clinical document architecture. A representation of vital signs that is compliant with the International Standards Organization 11073 standard is also discussed.
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TL;DR: MixMapper as discussed by the authors is a two-phase approach to infer admixture using moment statistics, first building an unadmixed scaffold tree and then adding admixed populations by solving systems of equations that express allele frequency divergences in terms of mixture parameters.
Abstract: The recent explosion in available genetic data has led to significant advances in understanding the demographic histories of and relationships among human populations. It is still a challenge, however, to infer reliable parameter values for complicated models involving many populations. Here we present MixMapper, an efficient, interactive method for constructing phylogenetic trees including admixture events using single nucleotide polymorphism (SNP) genotype data. MixMapper implements a novel two-phase approach to admixture inference using moment statistics, first building an unadmixed scaffold tree and then adding admixed populations by solving systems of equations that express allele frequency divergences in terms of mixture parameters. Importantly, all features of the model, including topology, sources of gene flow, branch lengths, and mixture proportions, are optimized automatically from the data and include estimates of statistical uncertainty. MixMapper also uses a new method to express branch lengths in easily interpretable drift units. We apply MixMapper to recently published data for HGDP individuals genotyped on a SNP array designed especially for use in population genetics studies, obtaining confident results for 30 populations, 20 of them admixed. Notably, we confirm a signal of ancient admixture in European populations---including previously undetected admixture in Sardinians and Basques---involving a proportion of 20--40% ancient northern Eurasian ancestry.
01 Jan 2012
TL;DR: This paper aims to demonstrate the efforts towards in-situ applicability of the MPI for Evolutionary Anthropology, as to provide real-time information about an individual’s TSP.
Abstract: 5 Department of Aesthetics and Communication, Aarhus University, Aarhus 6 Department of Biological Sciences, University of Botswana 7 Institute of Global Studies, Tokyo University of Foreign Studies, Tokyo 8 Department of Mathematics and Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge 9 Departments of Biology and Genetics, University of Pennsylvania, Philadelphia 10 23andMe, Inc., Mountain View 11 Department of Genetics, Stanford University, Palo Alto 12 Department of Evolutionary Genetics, MPI for Evolutionary Anthropology, Leipzig 13 Current affiliation: Laboratoire Dynamique du Langage, UMR5596, CNRS and Universite Lyon Lumiere 2 14 Current affiliation: Department of Evolutionary Genetics, MPI for Evolutionary Anthropology, Leipzig 15 Current affiliation: Department of Linguistics, MPI for Evolutionary Anthropology, Leipzig
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01 Nov 2012
TL;DR: A new weighted LD statistic is presented that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods and can discover phylogenetic relationships between populations by comparing weighted LD curves obained using a suite of references.
Abstract: Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese.
TL;DR: This corrects the article to show that the method used to derive the H2O2 “spatially aggregating force” is based on a two-step process, not a single step, like in the previous version of this paper.
Abstract: Nature 488, 370–374 (2012); doi:10.1038/nature11258 At the time of publication of this Letter, the authors were unaware of a manuscript arriving at broadly similar conclusions based on allotype analysis by Williams et al.1, which appeared in the American Journal of Physical Anthropology.
TL;DR: The authors summarizes the concerns of the anthropological community about Ashraf and Galor's (Forthcoming) article in the American Economic Review and presents a short reply summarizing the concerns expressed.
Abstract: This short reply summarizes the concerns of the anthropological community about Ashraf and Galor's (Forthcoming) article in the American Economic Review.
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14 May 2012
TL;DR: An elegant analysis of tens of thousands of patient records in an anesthesia information management system (AIMS) at a single institution provides convincing evidence that operations where the median estimated blood loss (EBL) is less than 50 ml do not require preoperative blood type and screen.
Abstract: D ESPITE vast stores of data in hospital information systems, there has been a dearth of analyses to provide rational criteria for preoperative laboratory testing. In this issue of ANESTHESIOLOGY, Dexter et al. perform an elegant analysis of tens of thousands of patient records in an anesthesia information management system (AIMS) at a single institution. They provide convincing evidence that operations where the median estimated blood loss (EBL) is less than 50 ml do not require preoperative blood type and screen. This moves beyond the traditional guidance from the American Association of Blood Banks (AABB) and others that a type-and-screen order is recommended for procedures that require less than 0.5 units of blood per patient per procedure. Although not specifically addressed in the study, this also brings into question the AABB principle that the Maximal Surgical Blood Ordering Schedule (MSBOS) should define the number of units needed to meet the needs of 80–90% of patients undergoing specific procedures. Despite a complex analysis, the authors provide a simple guide (table 2 of the paper) for perioperative teams to analyze their own data sets. Using simple spreadsheet software, it is relatively trivial to determine which scheduled procedures should be exempt from blood type and screen. The absence of an AIMS is not an impediment to performing this analysis in many hospitals that have computerized perioperative nursing records and blood banking systems. The American Society of Anesthesiologists has devoted extensive resources to promulgate Practice Guidelines for Perioperative Blood Transfusion and surveys of transfusion practices by anesthesiologists. We have not, however, taken an active role in facilitating universal implementation of a MSBOS in our facilities. Perhaps many of us believe that having an anesthesiologist representative on a hospital transfusion committee is sufficient, and that our blood-banking colleagues should lead this effort. This is unfortunate, because implementation of a MSBOS is highly cost-effective. One aspect of the MSBOS that has received less emphasis is the decision as to which procedures that will have not have blood cross-matched should require a preoperative blood type and screen. As Dexter et al. demonstrate, a huge proportion of this testing is wasted effort. Anesthesiologists and blood bank professionals have an obligation to use our expertise to create rational local guidelines for preoperative blood type and screen. Without detracting from the importance of this paper, there are several issues to highlight: cases with missing or erroneous EBL data, patients with preoperative anemia, and the possibility that a scheduled procedure will differ from the procedure performed. The documentation habits of the anesthesia care teams cast some doubt upon the data, since we cannot be certain that missing data are equivalent to minimal EBL in all cases. Although there is little doubt that patients with missing EBL were less likely to have high EBL or transfusion in the AIMS data studied, there is a question as to what extent the authors’ handling of the missing EBL data influenced the results. In