Author
Adam Auton
Other affiliations: Broad Institute, Cornell University, University of Oxford ...read more
Bio: Adam Auton is an academic researcher from Albert Einstein College of Medicine. The author has contributed to research in topics: Genome-wide association study & Population. The author has an hindex of 47, co-authored 94 publications receiving 51799 citations. Previous affiliations of Adam Auton include Broad Institute & Cornell University.
Papers published on a yearly basis
Papers
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TL;DR: Cov-LDSC is introduced, a method to accurately estimate genetic heritability and its enrichment in both homogenous and admixed populations with summary statistics and in-sample LD estimates, and develops a computationally efficient method to answer two specific questions.
Abstract: The increasing size and diversity of genome-wide association studies provide an exciting opportunity to study how the genetics of complex traits vary among diverse populations. Here, we introduce covariate-adjusted LD score regression (cov-LDSC), a method to accurately estimate genetic heritability and its enrichment in both homogenous and admixed populations with summary statistics and in-sample LD estimates. In-sample LD can be estimated from a subset of the GWAS samples, allowing our method to be applied efficiently to very large cohorts. In simulations, we show that unadjusted LDSC underestimates by 10% − 60% in admixed populations; in contrast, cov-LDSC is robust to all simulation parameters. We apply cov-LDSC to genotyping data from approximately 170,000 Latino, 47,000 African American and 135,000 European individuals. We estimate and detect heritability enrichment in three quantitative and five dichotomous phenotypes respectively, making this, to our knowledge, the most comprehensive heritability-based analysis of admixed individuals. Our results show that most traits have high concordance of and consistent tissue-specific heritability enrichment among different populations. However, for age at menarche, we observe population-specific heritability estimates of . We observe consistent patterns of tissue-specific heritability enrichment across populations; for example, in the limbic system for BMI, the per-standardized-annotation effect size τ* is 0.16 ± 0.04, 0.28 ± 0.11 and 0.18 ± 0.03 in Latino, African American and European populations respectively. Our results demonstrate that our approach is a powerful way to analyze genetic data for complex traits from underrepresented populations. Author summary Admixed populations such as African Americans and Hispanic Americans bear a disproportionately high burden of disease but remain underrepresented in current genetic studies. It is important to extend current methodological advancements for understanding the genetic basis of complex traits in homogeneous populations to individuals with admixed genetic backgrounds. Here, we develop a computationally efficient method to answer two specific questions. First, does genetic variation contribute to the same amount of phenotypic variation (heritability) across diverse populations? Second, are the genetic mechanisms shared among different populations? To answer these questions, we use our novel method to conduct the first comprehensive heritability-based analysis of a large number of admixed individuals. We show that there is a high degree of concordance in total heritability and tissue-specific enrichment between different ancestral groups. However, traits such as age at menarche show a noticeable differences among populations. Our work provides a powerful way to analyze genetic data in admixed populations and may contribute to the applicability of genomic medicine to admixed population groups.
12 citations
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Autonomous University of Barcelona1, Lundbeck2, Aarhus University3, Harvard University4, Broad Institute5, University of Bergen6, Utrecht University7, Radboud University Nijmegen8, Goethe University Frankfurt9, University of Würzburg10, Universidade Federal do Rio Grande do Sul11, Haukeland University Hospital12, I.M. Sechenov First Moscow State Medical University13, Maastricht University14, Oslo University Hospital15, University of Oslo16, Monash University17, University of Toronto18, Thomas Jefferson University19, Alfred I. duPont Hospital for Children20, University of Pennsylvania21, Children's Hospital of Philadelphia22, University Medical Center Groningen23, University of Duisburg-Essen24, Semel Institute for Neuroscience and Human Behavior25, Norwegian Institute of Public Health26, Emory University27, King's College London28, State University of New York Upstate Medical University29, Karolinska Institutet30, Örebro University31
TL;DR: It is confirmed that persistent ADHD in adults is a neurodevelopmental disorder and the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective is extended.
Abstract: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent genome-wide significant loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.
11 citations
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TL;DR: This paper performed a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2.
Abstract: Abstract Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2 . Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention.
9 citations
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University of Edinburgh1, Max Planck Society2, QIMR Berghofer Medical Research Institute3, Shaanxi Normal University4, University of St Andrews5, Tufts University6, University of Oxford7, Yale University8, University of Colorado Boulder9, University of Denver10, University of Nebraska Medical Center11, University of Queensland12
TL;DR: This article found 42 independent genome-wide significant loci: 17 are in genes linked to or pleiotropic with cognitive ability/educational attainment; 25 are novel and may be more specifically associated with dyslexia.
Abstract: Reading and writing are crucial for many aspects of modern life but up to 1 in 10 children are affected by dyslexia [1, 2], which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70% [3, 4], yet no convincing genetic markers have been found due to limited study power [5]. Here, we present a genome-wide association study representing a 20-fold increase in sample size from prior work, with 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls. We identified 42 independent genome-wide significant loci: 17 are in genes linked to or pleiotropic with cognitive ability/educational attainment; 25 are novel and may be more specifically associated with dyslexia. Twenty-three loci (12 novel) were validated in independent cohorts of Chinese and European ancestry. We confirmed a similar genetic aetiology of dyslexia between sexes, and found genetic covariance with many traits, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Causal analyses revealed a directional effect of dyslexia on attention deficit hyperactivity disorder and bidirectional effects on socio-educational traits but these relationships require further investigation. Dyslexia polygenic scores explained up to 6% of variance in reading traits in independent cohorts, and might in future enable earlier identification and remediation of dyslexia.
9 citations
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University of Cambridge1, Harvard University2, Broad Institute3, Science for Life Laboratory4, Wellcome Trust Sanger Institute5, University of Shizuoka6, Amgen7, Western General Hospital8, Institute of Cancer Research9, Uppsala University10, Johns Hopkins University School of Medicine11, University of Tokyo12, Royal Devon and Exeter Hospital13, Gdańsk Medical University14, University of Iceland15, University of Birmingham16, Queen Mary University of London17, Kyoto University18, University of Copenhagen19, Brigham and Women's Hospital20
TL;DR: This research has been conducted using the UK Biobank Resource under application 9905 and 19808 and was supported by the Medical Research Council [Unit Programme number MC_UU_12015/2].
Abstract: This research has been conducted using the UK Biobank Resource under application 9905 and 19808. This work was supported by the Medical Research Council [Unit Programme number MC_UU_12015/2]. Full study-specific and individual acknowledgements can be found in the supplementary information.
8 citations
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TL;DR: Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
Abstract: As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
37,898 citations
28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
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TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
12,661 citations
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TL;DR: In this article, the authors present an approach for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
Abstract: Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.
10,798 citations
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TL;DR: VCFtools is a software suite that implements various utilities for processing VCF files, including validation, merging, comparing and also provides a general Perl API.
Abstract: Summary: The variant call format (VCF) is a generic format for storing DNA polymorphism data such as SNPs, insertions, deletions and structural variants, together with rich annotations. VCF is usually stored in a compressed manner and can be indexed for fast data retrieval of variants from a range of positions on the reference genome. The format was developed for the 1000 Genomes Project, and has also been adopted by other projects such as UK10K, dbSNP and the NHLBI Exome Project. VCFtools is a software suite that implements various utilities for processing VCF files, including validation, merging, comparing and also provides a general Perl API.
Availability: http://vcftools.sourceforge.net
Contact: [email protected]
10,164 citations