Author
Jane Z. Kuo
Other affiliations: UCLA Medical Center, Los Angeles Biomedical Research Institute, Princeton University ...read more
Bio: Jane Z. Kuo is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Genome-wide association study & Diabetic retinopathy. The author has an hindex of 18, co-authored 24 publications receiving 1754 citations. Previous affiliations of Jane Z. Kuo include UCLA Medical Center & Los Angeles Biomedical Research Institute.
Papers
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University of Washington1, National University of Singapore2, Cedars-Sinai Medical Center3, National Institutes of Health4, Erasmus University Rotterdam5, University of Newcastle6, University of Wisconsin-Madison7, University of Iceland8, University of Texas Health Science Center at Houston9, University of Melbourne10, University of Sydney11, Boston University12, University of Auckland13, Group Health Cooperative14, University of Amsterdam15, Singapore National Eye Center16, Agency for Science, Technology and Research17, University of California, San Francisco18, University of Michigan19, Harvard University20
TL;DR: This genome-wide association study of retinopathy in individuals without diabetes showed little evidence of genetic associations and further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.
Abstract: Background
Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes.
805 citations
University of Pennsylvania1, University of Helsinki2, University of Cambridge3, Stanford University4, Lund University5, McMaster University6, University of Tokyo7, Imperial College London8, National University of Singapore9, University of Oklahoma Health Sciences Center10, Icahn School of Medicine at Mount Sinai11, Punjab Institute of Cardiology12, Karachi Institute of Heart Diseases13, Civil Hospital Karachi14, Liaquat National Hospital15, King Edward Medical University16, Lahore General Hospital17, All India Institute of Medical Sciences18, Los Angeles Biomedical Research Institute19, National Health Research Institutes20, National Taiwan University21, National Defense Medical Center22, International Centre for Diarrhoeal Disease Research, Bangladesh23, MedStar Washington Hospital Center24, Frederiksberg Hospital25, Copenhagen University Hospital26, Leiden University Medical Center27, University of Glasgow28, Columbia University29, National Institutes of Health30
TL;DR: A genome-wide, multi-ancestry study of genetic variation for type 2 diabetes and coronary heart disease finds variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.
Abstract: Danish Saleheen, Benjamin Voight and colleagues perform genome-wide analysis of multi-ancestry cohorts to identify genetic associations with type 2 diabetes (T2D) and coronary heart disease (CHD). They find novel loci and show that 24% of T2D loci are also associated with CHD and that greater genetic risk of T2D increases risk of CHD. To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D–CHD analysis identified eight variants—two of which are coding—where T2D and CHD associations appear to colocalize, including a new joint T2D–CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.
193 citations
Vanderbilt University1, Tokyo Medical and Dental University2, Kyoto University3, Agency for Science, Technology and Research4, Chinese Academy of Sciences5, Asia University (Taiwan)6, Guangxi Medical University7, Tulane University8, University of North Carolina at Chapel Hill9, Huazhong University of Science and Technology10, Shanghai Jiao Tong University11, Xuzhou Medical College12, Los Angeles Biomedical Research Institute13, National Defense Medical Center14, Kyushu University15, Shiga University of Medical Science16, China Medical University (Taiwan)17, University of San Carlos18, Peking Union Medical College19, Tsinghua University20, Chung Shan Medical University21, Hallym University22, Academia Sinica23, Washington University in St. Louis24, Tunghai University25, Shimane University26, Yokohama City University27, University of California, San Francisco28, University of Texas at Austin29, National University of Singapore30, Centers for Disease Control and Prevention31, New Generation University College32, Singapore National Eye Center33, National Health Research Institutes34, National Taiwan University35, Hanyang University36, Harvard University37, Chonnam National University38, Wonkwang University39, Keimyung University40, Kyungpook National University41, Taipei Veterans General Hospital42, Stanford University43, University of California, San Diego44, Ehime University45
TL;DR: A meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals finds the association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women.
Abstract: Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.
176 citations
TL;DR: A thorough literature review of the genetic factors for diabetic retinopathy, including heritability scores, twin studies, family studies, candidate gene studies, linkage studies, and genome-wide association studies (GWASs) found that the field of DR genetics is still in its infancy.
Abstract: Importance In the past decade, significant progress in genomic medicine and technologic developments has revolutionized our approach to common complex disorders in many areas of medicine, including ophthalmology. A disorder that still needs major genetic progress is diabetic retinopathy (DR), one of the leading causes of blindness in adults. Objective To perform a literature review, present the current findings, and highlight some key challenges in DR genetics. Design, Setting, and Participants We performed a thorough literature review of the genetic factors for DR, including heritability scores, twin studies, family studies, candidate gene studies, linkage studies, and genome-wide association studies (GWASs). Main Outcome Measures Environmental and genetic factors for DR. Results Although there is clear demonstration of a genetic contribution in the development and progression of DR, the identification of susceptibility loci through candidate gene approaches, linkage studies, and GWASs is still in its infancy. The greatest obstacles remain a lack of power because of small sample size of available studies and a lack of phenotype standardization. Conclusions and Relevance The field of DR genetics is still in its infancy and is a challenge because of the complexity of the disease. This review outlines some strategies and lessons for future investigation to improve our understanding of this complex genetic disorder.
94 citations
TL;DR: The finding nominates possible novel loci as potential DR susceptibility genes in the Chinese that are independent of the level of HbA1c and duration of diabetes and may provide insight into the pathophysiology of DR.
Abstract: Diabetic retinopathy (DR) is a leading cause of preventable blindness in adults. To identify genetic contributions in DR, we studied 2071 type 2 diabetics. We first conducted a genome-wide association study of 1007 individuals, comparing 570 subjects with ≥8 years duration without DR (controls) with 437 PDR (cases) in the Chinese discovery cohort. Cases and controls were similar for HbA1c, diabetes duration and body mass index. Association analysis with imputed data identified three novel loci: TBC1D4-COMMD6-UCHL3 (rs9565164, P = 1.3 × 10−7), LRP2-BBS5 (rs1399634, P = 2.0 × 10−6) and ARL4C-SH3BP4 (rs2380261, P = 2.1 × 10−6). Analysis of an independent cohort of 585 Hispanics diabetics with or without DR though did not confirm these signals. These genes are still of particular interest because they are involved in insulin regulation, inflammation, lipid signaling and apoptosis pathways, all of which are possibly involved with DR. Our finding nominates possible novel loci as potential DR susceptibility genes in the Chinese that are independent of the level of HbA1c and duration of diabetes and may provide insight into the pathophysiology of DR.
87 citations
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01 Jan 2014
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care.
Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.
9,618 citations
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01 Feb 2009
TL;DR: This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale, and what might be coming next.
Abstract: Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?
5,234 citations
TL;DR: The fundamental concepts of enhanced permeability and retention effect (EPR) are revisited and the mechanisms proposed to enhance preferential "retention" in the tumor, whether using active targeting of nanoparticles, binding of drugs to their tumoral targets or the presence of tumor associated macrophages are explored.
2,199 citations
Broad Institute1, Harvard University2, University of California, Los Angeles3, VU University Medical Center4, VU University Amsterdam5, North Carolina State University6, Karolinska Institutet7, University of North Carolina at Chapel Hill8, University of Tampere9, Turku University Hospital10, University of Turku11, University of Eastern Finland12
TL;DR: A powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated with complex traits is introduced.
Abstract: Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance of one or multiple proteins. Here we introduce a powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated with complex traits. We leverage expression imputation from genetic data to perform a transcriptome-wide association study (TWAS) to identify significant expression-trait associations. We applied our approaches to expression data from blood and adipose tissue measured in ∼ 3,000 individuals overall. We imputed gene expression into GWAS data from over 900,000 phenotype measurements to identify 69 new genes significantly associated with obesity-related traits (BMI, lipids and height). Many of these genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits.
1,473 citations
University of Oxford1, University of Michigan2, Wellcome Trust Sanger Institute3, Amgen4, University of Cambridge5, University of Copenhagen6, University of Liverpool7, University of Freiburg8, Boston University9, University of Tartu10, Erasmus University Medical Center11, Leiden University Medical Center12, Pasteur Institute13, Icahn School of Medicine at Mount Sinai14, UCLA Medical Center15, Vanderbilt University Medical Center16, Wake Forest University17, National University of Singapore18, Imperial College London19, London North West Healthcare NHS Trust20, Charité21, Innsbruck Medical University22, Washington University in St. Louis23, Queen Mary University of London24, University of Southern Denmark25, National and Kapodistrian University of Athens26, Robertson Centre for Biostatistics27, University of Exeter28, Uppsala University29, University of Düsseldorf30, Steno Diabetes Center31, Aalborg University32, University of Eastern Finland33, Broad Institute34, Frederiksberg Hospital35, Lund University36, University of Bergen37, Technische Universität München38, University of North Carolina at Chapel Hill39, University of Edinburgh40, Ninewells Hospital41, University of Minnesota42, University of Glasgow43, Ludwig Maximilian University of Munich44, University of Iceland45, Aarhus University46, Science for Life Laboratory47, Stanford University48, University of Helsinki49, National Institutes of Health50, University of Dundee51, Harvard University52
TL;DR: Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.
Abstract: We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency 2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).
1,136 citations