Target discovery using biobanks and human genetics.

[1]  Tanya M. Teslovich,et al.  Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls , 2019, Nature.

[2]  Michael V Holmes,et al.  Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China , 2019, The Lancet.

[3]  J. Venter,et al.  Functional characterization of 3D protein structures informed by human genetic diversity , 2019, Proceedings of the National Academy of Sciences.

[4]  Gonçalo Abecasis,et al.  Whole exome sequencing and characterization of coding variation in 49,960 individuals in the UK Biobank , 2019, bioRxiv.

[5]  Dermot F. Reilly,et al.  Phenome-wide association studies across large population cohorts support drug target validation , 2018, Nature Communications.

[6]  Kai Wang,et al.  Next-generation sequencing in drug development: target identification and genetically stratified clinical trials. , 2018, Drug discovery today.

[7]  Jay Shendure,et al.  A Multiplex Homology-Directed DNA Repair Assay Reveals the Impact of More Than 1,000 BRCA1 Missense Substitution Variants on Protein Function. , 2018, American journal of human genetics.

[8]  D. Fu,et al.  Highly specific monoclonal antibodies for allosteric inhibition and immunodetection of the human pancreatic zinc transporter ZnT8 , 2018, The Journal of Biological Chemistry.

[9]  Frederick P. Roth,et al.  Multiplexed assays of variant effects contribute to a growing genotype–phenotype atlas , 2018, Human Genetics.

[10]  Yi Zhang,et al.  Performance evaluation of pathogenicity-computation methods for missense variants , 2018, Nucleic acids research.

[11]  G. Rutter,et al.  Mice harboring the human SLC30A8 R138X loss-of-function mutation have increased insulin secretory capacity , 2018, Proceedings of the National Academy of Sciences.

[12]  T. Kiernan,et al.  PCSK9 inhibitors and LDL reduction: pharmacology, clinical implications, and future perspectives , 2018, Expert review of cardiovascular therapy.

[13]  M. Rivas,et al.  Large-Scale Phenome-Wide Association Study of PCSK9 Variants Demonstrates Protection Against Ischemic Stroke , 2018, Circulation. Genomic and precision medicine.

[14]  S. Fazio,et al.  PCSK9: From Basic Science Discoveries to Clinical Trials , 2018, Circulation research.

[15]  Mary E. Haas,et al.  Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease , 2018, Nature Communications.

[16]  Amalio Telenti,et al.  Identification of misclassified ClinVar variants using disease population prevalence , 2016, bioRxiv.

[17]  Julia M. Barbarino,et al.  PharmGKB: A worldwide resource for pharmacogenomic information , 2018, Wiley interdisciplinary reviews. Systems biology and medicine.

[18]  W. Hiatt,et al.  PCSK9 Inhibitors: Mechanisms of Action, Metabolic Effects, and Clinical Outcomes. , 2018, Annual review of medicine.

[19]  David J. Nicholls,et al.  Impact of a five-dimensional framework on R&D productivity at AstraZeneca , 2018, Nature Reviews Drug Discovery.

[20]  Vanessa E. Gray,et al.  Multiplex Assessment of Protein Variant Abundance by Massively Parallel Sequencing , 2018, Nature Genetics.

[21]  Elizabeth Brunk,et al.  Mapping genetic variations to three-dimensional protein structures to enhance variant interpretation: a proposed framework , 2017, Genome Medicine.

[22]  C. Greenwood,et al.  Genetic architecture: the shape of the genetic contribution to human traits and disease , 2017, Nature Reviews Genetics.

[23]  Atina G. Coté,et al.  A framework for exhaustively mapping functional missense variants , 2017, Molecular systems biology.

[24]  Chunlei Liu,et al.  ClinVar: improving access to variant interpretations and supporting evidence , 2017, Nucleic Acids Res..

[25]  E. Green,et al.  Prioritizing diversity in human genomics research , 2017, Nature Reviews Genetics.

[26]  Maitreya J. Dunham,et al.  Variant Interpretation: Functional Assays to the Rescue. , 2017, American journal of human genetics.

[27]  Christopher M. DeBoever,et al.  Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study , 2017, bioRxiv.

[28]  Rachel G Liao,et al.  A Loss-of-Function Splice Acceptor Variant in IGF2 Is Protective for Type 2 Diabetes , 2017, Diabetes.

[29]  A. Peterson,et al.  Discovery of a cryptic peptide-binding site on PCSK9 and design of antagonists , 2017, Nature Structural &Molecular Biology.

[30]  K. Eilbeck,et al.  Settling the score: variant prioritization and Mendelian disease , 2017, Nature Reviews Genetics.

[31]  P. Visscher,et al.  10 Years of GWAS Discovery: Biology, Function, and Translation. , 2017, American journal of human genetics.

[32]  Daniel J. Park,et al.  Variant effect prediction tools assessed using independent, functional assay-based datasets: implications for discovery and diagnostics , 2017, Human Genomics.

[33]  Yajnavalka Banerjee,et al.  A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. , 2017, The New England journal of medicine.

[34]  P. Stenson,et al.  The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies , 2017, Human Genetics.

[35]  Daniel G. MacArthur,et al.  Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity , 2017, Nature.

[36]  A. Khera,et al.  Genetics of coronary artery disease: discovery, biology and clinical translation , 2017, Nature Reviews Genetics.

[37]  Neeraj Shah,et al.  PCSK9 inhibitors: A new era of lipid lowering therapy , 2017, World journal of cardiology.

[38]  Hynek Pikhart,et al.  PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study , 2017, The lancet. Diabetes & endocrinology.

[39]  K. Nasir,et al.  Economic Evaluation of PCSK9 Inhibitors in Reducing Cardiovascular Risk from Health System and Private Payer Perspectives , 2017, PloS one.

[40]  D. Cacchiarelli,et al.  Phenotypic Characterization of a Comprehensive Set of MAPK1/ERK2 Missense Mutants. , 2016, Cell reports.

[41]  S. Fullerton,et al.  Genomics is failing on diversity , 2016, Nature.

[42]  Inês Barroso,et al.  Prospective functional classification of all possible missense variants in PPARG , 2016, Nature Genetics.

[43]  D. MacArthur,et al.  Using high-resolution variant frequencies to empower clinical genome interpretation , 2016, Genetics in Medicine.

[44]  Levi C. T. Pierce,et al.  Deep sequencing of 10,000 human genomes , 2016, Proceedings of the National Academy of Sciences.

[45]  R. Collins,et al.  A phenome-wide association study of a lipoprotein-associated phospholipase A2 loss-of-function variant in 90 000 Chinese adults , 2016, International Journal of Epidemiology.

[46]  Dana C. Crawford,et al.  Unravelling the human genome–phenome relationship using phenome-wide association studies , 2016, Nature Reviews Genetics.

[47]  James Y. Zou.  Analysis of protein-coding genetic variation in 60,706 humans , 2015, Nature.

[48]  Eric J. Topol,et al.  Protective alleles and modifier variants in human health and disease , 2015, Nature Reviews Genetics.

[49]  Jennifer G. Robinson,et al.  Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. , 2015, The New England journal of medicine.

[50]  Jennifer G. Robinson,et al.  Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. , 2015, The New England journal of medicine.

[51]  David L. Young,et al.  Massively Parallel Functional Analysis of BRCA1 RING Domain Variants , 2015, Genetics.

[52]  Karsten M. Borgwardt,et al.  The Evaluation of Tools Used to Predict the Impact of Missense Variants Is Hindered by Two Types of Circularity , 2015, Human mutation.

[53]  J. Goldstein,et al.  A Century of Cholesterol and Coronaries: From Plaques to Genes to Statins , 2015, Cell.

[54]  P. Elliott,et al.  UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age , 2015, PLoS medicine.

[55]  Solid-Timi Investigators.  Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial. , 2014 .

[56]  M. Pangalos,et al.  Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework , 2014, Nature Reviews Drug Discovery.

[57]  P. Pais,et al.  Darapladib for preventing ischemic events in stable coronary heart disease. , 2014, The New England journal of medicine.

[58]  Thomas Meitinger,et al.  Loss-of-function mutations in SLC30A8 protect against type 2 diabetes , 2014, Nature Genetics.

[59]  M. Yacoub,et al.  The discovery of PCSK9 inhibitors: A tale of creativity and multifaceted translational research , 2013, Global cardiology science & practice.

[60]  Melissa A. Basford,et al.  Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data , 2013, Nature Biotechnology.

[61]  K. Boycott,et al.  Rare-disease genetics in the era of next-generation sequencing: discovery to translation , 2013, Nature Reviews Genetics.

[62]  D. Altshuler,et al.  Validating therapeutic targets through human genetics , 2013, Nature Reviews Drug Discovery.

[63]  G. Rutter,et al.  Animal Models of GWAS-Identified Type 2 Diabetes Genes , 2013, Journal of diabetes research.

[64]  Thomas Meitinger,et al.  Calmodulin Mutations Associated With Recurrent Cardiac Arrest in Infants , 2013, Circulation.

[65]  R. O’Brien,et al.  The Physiological Effects of Deleting the Mouse Slc30a8 Gene Encoding Zinc Transporter-8 Are Influenced by Gender and Genetic Background , 2012, PloS one.

[66]  M. Wheeler,et al.  Effects of high-fat diet feeding on Znt8-null mice: differences between β-cell and global knockout of Znt8. , 2012, American journal of physiology. Endocrinology and metabolism.

[67]  H. Prokisch,et al.  Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway. , 2011, American journal of human genetics.

[68]  J. Danesh,et al.  Lipoprotein‐associated phospholipase A2 activity and mass in relation to vascular disease and nonvascular mortality , 2010, Journal of internal medicine.

[69]  J. Danesh,et al.  Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies , 2010, The Lancet.

[70]  G. Rutter,et al.  Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion , 2010, Diabetologia.

[71]  Marylyn D. Ritchie,et al.  PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene–disease associations , 2010, Bioinform..

[72]  C. Eng,et al.  PTEN hamartoma tumor syndrome: An overview , 2009, Genetics in Medicine.

[73]  M. Granvik,et al.  Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice , 2009, Proceedings of the National Academy of Sciences.

[74]  Richard K P Benninger,et al.  Deletion of the mouse Slc30a8 gene encoding zinc transporter-8 results in impaired insulin secretion. , 2009, The Biochemical journal.

[75]  J. Brosens,et al.  TBX22 missense mutations found in patients with X-linked cleft palate affect DNA binding, sumoylation, and transcriptional repression. , 2007, American journal of human genetics.

[76]  J. Goldstein,et al.  Lowering LDL--Not Only How Low, But How Long? , 2006, Science.

[77]  Jonathan C. Cohen,et al.  Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. , 2006, The New England journal of medicine.

[78]  R. Hammer,et al.  Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[79]  Alexander Pertsemlidis,et al.  Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9 , 2005, Nature Genetics.

[80]  J. Weissenbach,et al.  Mutations in PCSK9 cause autosomal dominant hypercholesterolemia , 2003, Nature Genetics.

[81]  Eric S. Lander,et al.  The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes , 2000, Nature Genetics.

[82]  Peter A Merkel,et al.  Clinical research for rare disease: opportunities, challenges, and solutions. , 2009, Molecular genetics and metabolism.

[83]  Mulin Jun Li,et al.  Nature Genetics Advance Online Publication a N a Ly S I S the Support of Human Genetic Evidence for Approved Drug Indications , 2022 .