Validating therapeutic targets through human genetics

Phenotypic vs. Target-Based Drug Discovery for First-in-Class Medicines

(2013) D C Swinney   CLINICAL PHARMACOLOGY & THERAPEUTICS

Human Genetics in Rheumatoid Arthritis Guides a High-Throughput Drug Screen of the CD40 Signaling Pathway

(2013) Gang Li et al.   PLoS Genetics

Five Years of GWAS Discovery

(2012) Peter M. Visscher et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Low-Density Lipoprotein Receptor Gene Familial Hypercholesterolemia Variant Database: Update and Pathological Assessment

(2012) Ebele Usifo et al.   ANNALS OF HUMAN GENETICS

Therapeutic targeting of the complement system in age-related macular degeneration: a review

(2012) Robyn Troutbeck et al.   CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY

Inhibiting Alternative Pathway Complement Activation by Targeting the Factor D Exosite

(2012) Kenneth J. Katschke et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Will Cholesteryl Ester Transfer Protein Inhibition Succeed Primarily by Lowering Low-Density Lipoprotein Cholesterol?

(2012) Sekar Kathiresan   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial

(2012) Evan A Stein et al.   LANCET

Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study

(2012) Benjamin F Voight et al.   LANCET

The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis

(2012)   LANCET

A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline

(2012) Thorlakur Jonsson et al.   NATURE

Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease

(2012) Luke Jostins et al.   NATURE

Use of genome-wide association studies for drug repositioning

(2012) Philippe Sanseau et al.   NATURE BIOTECHNOLOGY

High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

(2012) Steve Eyre et al.   NATURE GENETICS

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

(2012) Karol Estrada et al.   NATURE GENETICS

Genetics of gene expression in primary immune cells identifies cell type–specific master regulators and roles of HLA alleles

(2012) Benjamin P Fairfax et al.   NATURE GENETICS

Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis

(2012) Eli A Stahl et al.   NATURE GENETICS

Chromatin marks identify critical cell types for fine mapping complex trait variants

(2012) Gosia Trynka et al.   NATURE GENETICS

Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

(2012) Lam C Tsoi et al.   NATURE GENETICS

Cholesterol-lowering blockbuster candidates speed into Phase III trials

(2012) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

Diagnosing the decline in pharmaceutical R&D efficiency

(2012) Jack W. Scannell et al.   NATURE REVIEWS DRUG DISCOVERY

Amyloid precursor protein (APP) A673T mutation in the elderly Finnish population

(2012) Mia Kero et al.   NEUROBIOLOGY OF AGING

Placebo-Controlled Trial of Tofacitinib Monotherapy in Rheumatoid Arthritis

(2012) Roy Fleischmann et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tofacitinib or Adalimumab versus Placebo in Rheumatoid Arthritis

(2012) Ronald F. van Vollenhoven et al.   NEW ENGLAND JOURNAL OF MEDICINE

Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol

(2012) Evan A. Stein et al.   NEW ENGLAND JOURNAL OF MEDICINE

A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes

(2012) D. G. MacArthur et al.   SCIENCE

Integrating Autoimmune Risk Loci with Gene-Expression Data Identifies Specific Pathogenic Immune Cell Subsets

(2011) Xinli Hu et al.   AMERICAN JOURNAL OF HUMAN GENETICS

What makes a good drug target?

(2011) Isabella Gashaw et al.   DRUG DISCOVERY TODAY

An overview of international literature from cystic fibrosis registries. Part 3. Disease incidence, genotype/phenotype correlation, microbiology, pregnancy, clinical complications, lung transplantation, and miscellanea

(2011) Donatello Salvatore et al.   Journal of Cystic Fibrosis

A rare penetrant mutation in CFH confers high risk of age-related macular degeneration

(2011) Soumya Raychaudhuri et al.   NATURE GENETICS

Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease

(2011) Manuel A Rivas et al.   NATURE GENETICS

Phase II failures: 2008–2010

(2011) John Arrowsmith   NATURE REVIEWS DRUG DISCOVERY

A CFTR Potentiator in Patients with Cystic Fibrosis and theG551DMutation

(2011) Bonnie W. Ramsey et al.   NEW ENGLAND JOURNAL OF MEDICINE

Cholesteryl ester transfer protein inhibition to reduce cardiovascular risk: where are we now?

(2011) Philip Barter et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology

(2011) Elizabeth J. Rossin et al.   PLoS Genetics

Riluzole pharmacokinetics in young patients with spinal muscular atrophy

(2010) Chadi Abbara et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Progress and Promise of Genome-Wide Association Studies for Human Complex Trait Genetics

(2010) B. E. Stranger et al.   GENETICS

Spinal muscular atrophy: mechanisms and therapeutic strategies

(2010) C. L. Lorson et al.   HUMAN MOLECULAR GENETICS

Etiology of Type 1 Diabetes

(2010) John A. Todd   IMMUNITY

A method and server for predicting damaging missense mutations

(2010) Ivan A Adzhubei et al.   NATURE METHODS

Competitiveness in follow-on drug R&D: a race or imitation?

(2010) Joseph A. DiMasi et al.   NATURE REVIEWS DRUG DISCOVERY

Uncovering the roles of rare variants in common disease through whole-genome sequencing

(2010) Elizabeth T. Cirulli et al.   NATURE REVIEWS GENETICS

Network medicine: a network-based approach to human disease

(2010) Albert-László Barabási et al.   NATURE REVIEWS GENETICS

New Therapeutic Approaches to Mendelian Disorders

(2010) Harry C. Dietz   NEW ENGLAND JOURNAL OF MEDICINE

Trait-Associated SNPs Are More Likely to Be eQTLs: Annotation to Enhance Discovery from GWAS

(2010) Dan L. Nicolae et al.   PLoS Genetics

Laminopathies and the long strange trip from basic cell biology to therapy

(2009) Howard J. Worman et al.   JOURNAL OF CLINICAL INVESTIGATION

Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm

(2009) Prateek Kumar et al.   Nature Protocols

A network view of disease and compound screening

(2009) Eric E. Schadt et al.   NATURE REVIEWS DRUG DISCOVERY

Assessing the translatability of drug projects: what needs to be scored to predict success?

(2009) Martin Wehling   NATURE REVIEWS DRUG DISCOVERY

Potential etiologic and functional implications of genome-wide association loci for human diseases and traits

(2009) L. A. Hindorff et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Rare Variants of IFIH1, a Gene Implicated in Antiviral Responses, Protect Against Type 1 Diabetes

(2009) S. Nejentsev et al.   SCIENCE

Identifying Relationships among Genomic Disease Regions: Predicting Genes at Pathogenic SNP Associations and Rare Deletions

(2009) Soumya Raychaudhuri et al.   PLoS Genetics

Common SNPs in HMGCR in Micronesians and Whites Associated With LDL-Cholesterol Levels Affect Alternative Splicing of Exon13

(2008) Ralph Burkhardt et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

NaV1.7 Gain-of-Function Mutations as a Continuum: A1632E Displays Physiological Changes Associated with Erythromelalgia and Paroxysmal Extreme Pain Disorder Mutations and Produces Symptoms of Both Disorders

(2008) M. Estacion et al.   JOURNAL OF NEUROSCIENCE

ProTx-II, a Selective Inhibitor of NaV1.7 Sodium Channels, Blocks Action Potential Propagation in Nociceptors

(2008) W. A. Schmalhofer et al.   MOLECULAR PHARMACOLOGY

Common variants at CD40 and other loci confer risk of rheumatoid arthritis

(2008) Soumya Raychaudhuri et al.   NATURE GENETICS

Common variants at 30 loci contribute to polygenic dyslipidemia

(2008) Sekar Kathiresan et al.   NATURE GENETICS

Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans

(2008) Sekar Kathiresan et al.   NATURE GENETICS

Genome-wide association studies for complex traits: consensus, uncertainty and challenges

(2008) Mark I. McCarthy et al.   NATURE REVIEWS GENETICS

Angiotensin II Blockade and Aortic-Root Dilation in Marfan's Syndrome

(2008) Benjamin S. Brooke et al.   NEW ENGLAND JOURNAL OF MEDICINE

Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of  -thalassemia

(2008) M. Uda et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

DNA polymorphisms at the BCL11A, HBS1L-MYB, and  -globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease

(2008) G. Lettre et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Genetic Mapping in Human Disease

(2008) D. Altshuler et al.   SCIENCE