Integrating common and rare genetic variation in diverse human populations
David Altshuler,Richard A. Gibbs,Leena Peltonen,Emmanouil T. Dermitzakis,Stephen F. Schaffner,Fuli Yu,Penelope E. Bonnen,de Bakker Piw.,Panagiotis Deloukas,Stacey Gabriel,R. Gwilliam,Sarah E. Hunt,Michael Inouye,Xiaoming Jia,Aarno Palotie,Melissa Parkin,Pamela Whittaker,Kyle Chang,Alicia Hawes,Lora Lewis,Yanru Ren,D Wheeler,Donna M. Muzny,Chris P. Barnes,Katayoon Darvishi,Matthew E. Hurles,Joshua M. Korn,K. Kristiansson,Charles Lee,S A McCarrol,James Nemesh,Alon Keinan,Stephen B. Montgomery,Samuela Pollack,Alkes L. Price,Nicole Soranzo,Claudia Gonzaga-Jauregui,Verneri Anttila,Wendy Brodeur,Mark J. Daly,Stephen Leslie,Gil McVean,Loukas Moutsianas,Huy Nguyen,Qingrun Zhang,Ghori Mjr.,Ralph McGinnis,William M. McLaren,Fumihiko Takeuchi,Sharon R. Grossman,Ilya Shlyakhter,Elizabeth Hostetter,Pardis C. Sabeti,Clement Adebamowo,Morris W. Foster,Deborah R. Gordon,Julio Licinio,M C Manca,Patricia A. Marshall,Ichiro Matsuda,D Ngare,Vivian Ota Wang,D Reddy,Charles N. Rotimi,Charmaine D.M. Royal,Richard R. Sharp,Changqing Zeng,Lisa D. Brooks,Jean E. McEwen +68 more
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TLDR
An expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.Abstract:
Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of <or=5%, and demonstrated the feasibility of imputing newly discovered CNPs and SNPs. This expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.read more
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Journal ArticleDOI
A Map of Human Genome Variation From Population-Scale Sequencing
Gonçalo R. Abecasis,David Altshuler,David Altshuler,Adam Auton,Lisa D Brooks,Richard Durbin,Richard A. Gibbs,Matthew E. Hurles,Gil McVean +8 more
TL;DR: The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype as mentioned in this paper, and the results of the pilot phase of the project, designed to develop and compare different strategies for genomewide sequencing with high-throughput platforms.
Journal ArticleDOI
From FastQ Data to High‐Confidence Variant Calls: The Genome Analysis Toolkit Best Practices Pipeline
Géraldine A. Van der Auwera,Mauricio O. Carneiro,Christopher Hartl,Ryan Poplin,Guillermo del Angel,Ami Levy-Moonshine,Tadeusz Jordan,Khalid Shakir,David Roazen,Joel Thibault,Eric Banks,Kiran V. Garimella,David Altshuler,Stacey Gabriel,Mark A. DePristo +14 more
TL;DR: This unit describes how to use BWA and the Genome Analysis Toolkit to map genome sequencing data to a reference and produce high‐quality variant calls that can be used in downstream analyses.
Journal ArticleDOI
The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
Kristin G. Ardlie,David S. DeLuca,Ayellet V. Segrè,Timothy J. Sullivan,Taylor Young,Ellen Gelfand,Casandra A. Trowbridge,Julian Maller,Taru Tukiainen,Monkol Lek,Lucas D. Ward,Pouya Kheradpour,Benjamin Iriarte,Yan Meng,Cameron D. Palmer,Tõnu Esko,Wendy Winckler,Joel N. Hirschhorn,Manolis Kellis,Daniel G. MacArthur,Gad Getz,Andrey A. Shabalin,Gen Li,Yi-Hui Zhou,Andrew B. Nobel,Ivan Rusyn,Fred A. Wright,Tuuli Lappalainen,Pedro G. Ferreira,Halit Ongen,Manuel A. Rivas,Alexis Battle,Sara Mostafavi,Jean Monlong,Michael Sammeth,Marta Melé,Ferran Reverter,Jakob M. Goldmann,Daphne Koller,Roderic Guigó,Mark I. McCarthy,Emmanouil T. Dermitzakis,Eric R. Gamazon,Hae Kyung Im,Anuar Konkashbaev,Dan L. Nicolae,Nancy J. Cox,Timothée Flutre,Xiaoquan Wen,Matthew Stephens,Jonathan K. Pritchard,Zhidong Tu,Bin Zhang,Tao Huang,Quan Long,Luan Lin,Jialiang Yang,Jun Zhu,Jun Liu,Amanda Brown,Bernadette Mestichelli,Denee Tidwell,Edmund Lo,Mike Salvatore,Saboor Shad,Jeffrey A. Thomas,John T. Lonsdale,Michael T. Moser,Bryan Gillard,Ellen Karasik,Kimberly Ramsey,Christopher Choi,Barbara A. Foster,John Syron,Johnell Fleming,Harold Magazine,Rick Hasz,Gary Walters,Jason Bridge,Mark Miklos,Susan L. Sullivan,Laura Barker,Heather M. Traino,Maghboeba Mosavel,Laura A. Siminoff,Dana R. Valley,Daniel C. Rohrer,Scott D. Jewell,Philip A. Branton,Leslie H. Sobin,Mary Barcus,Liqun Qi,Jeffrey McLean,Pushpa Hariharan,Ki Sung Um,Shenpei Wu,David Tabor,Charles Shive,Anna M. Smith,Stephen A. Buia,Anita H. Undale,Karna Robinson,Nancy Roche,Kimberly M. Valentino,Angela Britton,Robin Burges,Debra Bradbury,Kenneth W. Hambright,John Seleski,Greg E. Korzeniewski,Kenyon Erickson,Yvonne Marcus,Jorge Tejada,Mehran Taherian,Chunrong Lu,Margaret J. Basile,Deborah C. Mash,Simona Volpi,Jeffery P. Struewing,Gary F. Temple,Joy T. Boyer,Deborah Colantuoni,Roger Little,Susan E. Koester,Latarsha J. Carithers,Helen M. Moore,Ping Guan,Carolyn C. Compton,Sherilyn Sawyer,Joanne P. Demchok,Jimmie B. Vaught,Chana A. Rabiner,Nicole C. Lockhart +132 more
TL;DR: The landscape of gene expression across tissues is described, thousands of tissue-specific and shared regulatory expression quantitative trait loci (eQTL) variants are cataloged, complex network relationships are described, and signals from genome-wide association studies explained by eQTLs are identified.
Journal ArticleDOI
LD score regression distinguishes confounding from polygenicity in genome-wide association studies :
Brendan Bulik-Sullivan,Po-Ru Loh,Hilary K. Finucane,Stephan Ripke,Jian Yang,Nick Patterson,Mark J. Daly,Alkes L. Price,Benjamin M. Neale +8 more
TL;DR: It is found that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size, and the LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control.
Journal ArticleDOI
Systematic localization of common disease-associated variation in regulatory DNA.
Matthew T. Maurano,Richard Humbert,Eric Rynes,Robert E. Thurman,Eric Haugen,Hao Wang,Alex Reynolds,Richard Sandstrom,Hongzhu Qu,Hongzhu Qu,Jennifer A. Brody,Anthony Shafer,Fidencio Neri,Kristen Lee,Tanya Kutyavin,Sandra Stehling-Sun,Audra K. Johnson,Theresa K. Canfield,Erika Giste,Morgan Diegel,Daniel Bates,R. Scott Hansen,Shane Neph,Peter J. Sabo,Shelly Heimfeld,Antony Raubitschek,Steven F. Ziegler,Chris Cotsapas,Nona Sotoodehnia,Ian A. Glass,Shamil R. Sunyaev,Rajinder Kaul,John A. Stamatoyannopoulos +32 more
TL;DR: P pervasive involvement of regulatory DNA variation in common human disease and provide pathogenic insights into diverse disorders are suggested.
References
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Journal ArticleDOI
Biases and Reconciliation in Estimates of Linkage Disequilibrium in the Human Genome
Itsik Pe'er,Itsik Pe'er,Yves Chretien,Yves Chretien,Paul I.W. de Bakker,Jeffrey C. Barrett,Mark J. Daly,David Altshuler +7 more
TL;DR: Bias in estimations of linkage disequilibrium along the human genome and in the population under study are dissected to guide the understanding of empirical LD surveys and has implications for whole-genome association studies.
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