Food and drug administration fda, 10 biopharmaceutical companies, and multiple nonprofit. Also available are summary statistics for the transethnic t2d gwas metaanalysis as published in mahajan et al. Metaanalysis provides an efficient and practical strategy for detecting variants with modest effect sizes skol et al. Genomewide association analyses in 128,266 individuals.
We performed a meta analysis of 35 genome screens for 2dm, 36 for obesity or body mass index bmidefined obesity, and 21 for cad using genome search meta analysis gsma. Candidate drugs targeted for type 2 diabetes has been suggested in the approved drugs such as thiazolidinediones for rs1801282 andor unapproved drugs such as gck activators for rs10278336 through proteinprotein interaction data and therapeutic targets database using the gwas data for type 2 diabetes. Genotype imputation is carried out by statistical methods that combine the gwas data together with a. However, the benefitrisk balance of insulin remains controversial. Genetic association analysis of lars2 with type 2 diabetes. Effect of lifestyle intervention in patients with type 2. A metaanalysis of genomewide association studies for.
Metaanalysis approach identifies candidate genes and associated molecular networks for type2 diabetes mellitus axel rasche, 1 hadi alhasani, 2 and ralf herwig 1 1 maxplanckinstitute for molecular genetics, department of vertebrate genomics, ihnestrasse 6373, d14195 berlin, germany. Results from twin studies examining the genetic overlap between type 2 diabetes and depression are currently inconclusive. There is a need for developing systems biology approaches to integrate. Type 2 diabetes t2d is a heterogeneous disease for which 1 diseasecausing pathways are incompletely understood and 2 subclassification may improve patient management. Examination of all type 2 diabetes gwas loci reveals hhex. An expanded genomewide association study of type 2 diabetes. After correction for age and sex, we observed a strong association with type 2 diabetes for rs9939609 in hunt2. The aim of this meta analysis was to evaluate the effects of comprehensive lifestyle change, such as diet, exercise, and education, on clinical markers that are riskfactors for cardiovascular disease in patients with type 2 diabetes. Diabetes genetics replication and metaanalysis diagram consortium et al.
Type 2 diabetes t2d is a major public health problem whose global. Here we conduct a metaanalysis of genomewide association studies gwas with 16. Conclusions our doseresponse meta analysis of prospective studies shows a ushaped relationship between sleep duration and risk of type 2 diabetes, with the lowest type 2 diabetes risk at 78 h per day of sleep duration. Metaanalysis of genomewide association studies in african. When blood glucose targets are not achieved with diet and lifestyle intervention, insulin is recommended whether or not the patient is already taking hypoglycaemic drugs. Genomewide metaanalysis of genetic susceptible genes for type 2 diabetes paul j hale, 1, 2 alfredo m lopezyunez, 3 and jake y chen 1, 2, 4, 5 1 school of informatics, indiana universitypurdue university, indianapolis, in, usa.
It has become standard to measure the quality of imputation at each snp or indel via an information measure. Untyped hapmap2 snps were imputed using the impute2 software package. Unlike other biomarkers, germline genetic markers do not change with disease progression or treatment. Swaminathan abstract aims selfmonitoring of blood or urine glucose is widely used by subjects with type 2 diabetes mellitus.
To characterize type 2 diabetes t2dassociated variation across the allele frequency spectrum, we conducted a metaanalysis of genomewide. Genomewide association study for type 2 diabetes in indians. Objective a number of studies have found that bmi in early life influences the risk of developing type 2 diabetes later in life. This increase is linked to aging of the population, the rise of obesity, the change in diagnostic criteria of diabetes and more extensive screening. Gwas quality metrics including a test for parentoffspring transmission, hardyweinberg p gwas using an independent gwas metaanalysis dataset from. A twostage genome wide association study was conducted. Research design and methods we conducted a mendelian randomization mr analysis using summarylevel statistics from the largest published metaanalyses of genomewide association. Pdf genomewide metaanalysis of genetic susceptible genes. For testing reverse causality of type 2 diabetes on our sleep phenotypes, we used 55 of 65 common variants listed in s6 table known to be associated with type 2 diabetes at genome wide significance in a meta analysis of 34,840 cases and 114,981, excluding those known or suspected to be pleiotropic. Type 2 diabetes gwas metaanalysis in japanese population. Finemapping type 2 diabetes loci to singlevariant resolution using highdensity imputation and isletspecific epigenome maps. Research design and methods the current study included 2,591 participants with t2d and 3,052 participants without t2d of european ancestry from the nurses.
Meta analysis geneset enrichment of variant associations image credit. Metaanalysis geneset enrichment of variant associations image credit. Dec 17, 2012 many genetic studies, including single gene studies and genomewide association studies gwas, aim to identify risk alleles for genetic diseases such as type ii diabetes t2d. Metaanalysis of the risk of cataract in type 2 diabetes. Tcf7l2 gene polymorphisms and type 2 diabetes risk. Many genetic studies, including single gene studies and genomewide association studies gwas, aim to identify risk alleles for genetic diseases such as type ii diabetes t2d. Imputation is not a perfect process and sometimes snps and indels can be hard to impute. Our goal was to investigate if any type 2 diabetes variants uncovered through genomewide association studies gwas impact bmi in childhood. Novel risk genes identified in a genomewide association. Genomewide metaanalysis associates gpsm1 with type 2. Genetic predisposition to central obesity and risk of type 2. A genomewide integrative analysis of gwas and eqtls data. Genomewide association study for type 2 diabetes in.
A genomewide association study of type 2 diabetes michael boehnke department of biostatistics. T2dm poses a huge burden for the health care systems and is, thus, subject to intensive biomedical research. Objective this study tested the hypothesis that genetically raised hyperglycemia increases coronary artery disease cad risk separately from the risk conferred by type 2 diabetes as a whole. Genomewide association study of coronary artery calcified. Type 2 diabetes genetic loci informed by multitrait. Permanente national and northern california community benefit programs. Results relationship among fto, type 2 diabetes, and obesityrelated quantitative traits across life span in hunt. Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes t2d. New york genomeweb researchers have uncovered more than two dozen new genetic loci that are linked to type 2 diabetes in the. Metaanalysis supports ada guidelines for type 2 diabetes. Metaanalysis statistics and plots were produced using the metan module developed for stata and with gwama genomewide association metaanalysis software.
For access to these, please follow the links to the left. Metaanalysis supports ada guidelines for type 2 diabetes drugs. To further understanding of the genetic basis of type 2 diabetes t2d susceptibility, we aggregated published metaanalyses of genomewide association studies gwas, including 26,488 cases and 83,964 controls of european, east asian, south asian and mexican and mexican american ancestry. Fto, type 2 diabetes, and weight gain throughout adult. Whether there is shared genetic background underlying these diseases remained unclear. We validated the 23andme gwas using an independent gwas metaanalysis dataset from scott et al. Type 2 diabetes t2d is a very common disease in humans.
Integrative analysis of gwas and eqtls data was conducted by smr software. All statistical analyses were performed by stata 10. We aimed to examine whether there are common genetic factors between type 2 diabetes and depression in a sri lankan population using genetic modelfitting analysis. The smr single gene analysis results were further subjected to gene set enrichment analysis gsea for identifying obesity associated gene sets. Adiponectin is an adipocytesecreted protein and blood adiponectin levels are positively associated with high density lipoprotein cholesterol hdlc concentration and negatively correlated with the risk of type 2 diabetes t2d, glucose, insulin, insulin resistance, triglycerides and anthropometric measures of obesity. We performed a metaanalysis of 35 genome screens for 2dm, 36 for obesity or body mass index bmidefined obesity, and 21 for cad using genome search. The effect of lifestyle intervention on clinical risk factors in patients with type 2 diabetes is unclear. The forms below provide access to association summary statistics for the diagramv3 gwas metaanalysis, as published in morris et al 2012. Please note that the summary statistics presented in this file have not been corrected for a second round of genomic control after metaanalysis. Metaanalysis approach identifies candidate genes and. Gwas and meta analysis the approach gwas data quality model gwas data quality management tools conclusions. Stata and with gwama genomewide association metaanalysis software 24. Genomewide metaanalysis of genetic susceptible genes for type 2 diabetes. Genomewide metaanalysis of genetic susceptible genes for.
Genetically driven hyperglycemia increases risk of. Here we conduct a metaanalysis of genomewide association studies gwas with 16 million genetic variants in 62,892 t2d cases and 596,424 controls of european ancestry. In this study, we performed metaanalysis of 17 gwas in 8284 cases and. Genetic overlap between type 2 diabetes and depression in. To identify genetic factors contributing to type 2 diabetes t2d, we. Genomewide association analyses identify 143 risk variants and. Both short and long sleep duration are associated with a significantly increased risk of type 2 diabetes, underscoring the importance of appropriate sleep duration in the.
Magenta is a computational tool that tests for enrichment of genetic associations in predefined biological processes or sets of functionally related genes, using genomewide genetic data as input. P genomewide association analysis identifies loci for type 2 diabetes and. Metaanalysis bioinformatics tools gwas omicx omictools. To identify genetic factors contributing to type 2 diabetes t2d, we performed largescale metaanalyses by using a custom. Shows the potential of general purpose software to be used in the scientific area. This metaanalysis aimed to investigate the association between type 2 diabetes t2d and the risk of cataract. Compared with the nondiabetic population of the same age, allcause mortality. Dec 11, 2011 yoon shin cho, mark seielstad and colleagues report a meta analysis of genomewide association studies for type 2 diabetes in individuals of east asian ancestry. Objective abdominal obesity is a major risk factor for type 2 diabetes t2d. Genomewide association analyses identify 143 risk variants. The aim of this metaanalysis was to evaluate the effects of comprehensive lifestyle change, such as diet, exercise, and education, on clinical markers that are riskfactors for cardiovascular disease in patients with type 2 diabetes. Genetic predisposition to central obesity and risk of type.
Genomewide transancestry metaanalysis provides insight. Examination of all type 2 diabetes gwas loci reveals hhexide. Metaanalyses of genomewide association studies gwas have improved our understanding of the genetic foundations of a number of diseases, including diabetes. Author summary despite the higher prevalence of type 2 diabetes. Gwas have so far identified 129 loci associated with type 2 diabetes t2d. It is essential to anticipate and limit the social, economic and sanitary cost of type 2 diabetes t2d, which is in constant progression worldwide.
National and northern california community benefit programs. We further metaanalyzed the association of these variants with t2dm by. Guan w, pluzhnikov a, cox nj, boehnke m, for the international type 2 diabetes linkage analysis consortium metaanalysis of 23 type 2 diabetes linkage studies from the international type 2 diabetes linkage analysis consortium. Databases of pubmed, embase, and springerlink were retrieved for observational studies published before november 20. We conducted a twostage genomewide association study of t2d in 12,535 indians, a less explored but highrisk group.
Metaanalysis of genomewide association studies identifies 8 new. This question has not been addressed in nonwestern populations. The large number of previous studies into the genetic contribution to type 2 diabetes t2d make it a model phenotype for the application of gwas metaanalyses to further identify the genetics that underlie the phenotype 2, 3, 57. This process greatly increases the number of snps that can be tested for association, increases the power of the study, and facilitates metaanalysis of gwas across distinct cohorts. Largescale genecentric metaanalysis across 39 studies. Lauren solomon, broad communications, broad institute, cambridge, ma.
Cdkal1 rs7756992 and type 2 diabetes figure 2a presents the forest plot of risk allele or of an individual study and meta analysis for association between cdkal1 rs7756992 and type 2 diabetes in a total of 22,839 type 2 diabetes patients and 31,429 control subjects from the 21 studies. Summary of type 2 diabetes genes discovered in gwa studies in order of gene region. Type 2 diabetes t2d is a complex metabolic disease that affects 25. Fto, type 2 diabetes, and weight gain throughout adult life a. We selected a t2dm dataset from a gwas metaanalysis, and extracted 1971 snps.
Type 2 diabetes t2d is a complex disease affecting the worlds population at epidemic rates and whose pathophysiology remains incompletely understood. Diagram g gwas metaanalysis with adjustment for bmi stage 1 summary statistics published in in scott et al 2017 the data is made available as a tabseparated table enclosed in a zip file around 8 mb. The first stage metaanalysis of eight t2d genomewide association studies. Here we conduct a metaanalysis of genomewide association studies gwas with 16 million genetic variants in. An expanded genomewide association study of type 2 diabetes in europeans. Here we conduct a metaanalysis of genomewide association studies gwas with 16 million genetic variants in 62,892 t2d cases and. Validation of type 2 diabetes risk variants identified by genome. Type 2 diabetes 2dm, obesity, and coronary artery disease cad are frequently coexisted being as key components of metabolic syndrome. While extensive gwas have indicated that the effect sizes of common variants influencing type 2 diabetes risk are modest, the potential remains for lowfrequency variants to have effects on type 2 diabetes risk that are more substantial, which was corroborated by our previous observation regarding the h324q variant. Jul 27, 2018 type 2 diabetes t2d is a very common disease in humans. Identification of shared genetic susceptibility locus for. To identify genes associated with cac in aas with type 2 diabetes t2d, a genomewide association study gwas was performed using the illumina 5 m chip in 691 african americandiabetes heart study participants aadhs, with replication in 205 jackson heart study jhs participants with t2d.
The type 2 diabetes knowledge portal is being developed as part of the accelerating medicines partnership amp, a publicprivate partnership between the national institutes of health nih, the u. Research design and methods we conducted a mendelian randomization mr analysis using summarylevel statistics from the largest published metaanalyses of genomewide association studies gwas for. The eqtls dataset containing 927,753 eqtls was obtained from eqtls metaanalysis of 5,311 subjects. Genomewide metaanalysis of genetic susceptible genes for type 2 diabetes article pdf available in bmc systems biology 6suppl 3. The gwas for rheumatoid arthritis also indicated existing cancer drugs as novel candidates for rheumatoid arthritis using a similar strategy. To further understanding of the genetic basis of type 2 diabetes t2d susceptibility, we aggregated published metaanalyses of genomewide association studies gwas including 26,488 cases and 83,964 controls of european, east asian, south asian, and mexican and mexican american ancestry.
Most meta analysis of genomewide association studies is only possible due to imputation of genotypes. Metasoft is a metaanalysis software designed for performing a range of basic and advanced metaanalytic methods. S16 december 2012 with 106 reads how we measure reads. Detailed information about the content of the table is available in this pdf. We currently provide a list of diagram publications. For testing reverse causality of type 2 diabetes on our sleep phenotypes, we used 55 of 65 common variants listed in s6 table known to be associated with type 2 diabetes at genome wide significance in a metaanalysis of 34,840 cases and 114,981, excluding those known or suspected to be pleiotropic. Diamante european metaanalysis of type 2 diabetes 8th october 2018 reference. After correction for age and sex, we observed a strong association with.
Yoon shin cho, mark seielstad and colleagues report a metaanalysis of genomewide association studies for type 2 diabetes in individuals of east asian ancestry. Eleftheria zeggini on metaanalysis in genomewide association studies. However, in t2d studies, there is a significant amount of the hereditary risk that cannot be simply explained by individual risk genes. In 2030, according to the world health organization, 366 million people worldwide will live with type 2 diabetes t2d. Type2 diabetes mellitus t2dm is a rapidly increasing disease with more than 170 million afflicted persons worldwide constituting more than 90% of all diabetic patients. Genomewide association studies gwas have facilitated a substantial and rapid rise in the number of. Genetically driven hyperglycemia increases risk of coronary. We are releasing the summary data from our genomewide meta analyses of. Genomewide metaanalysis associates gpsm1 with type 2 diabetes, a plausible gene involved in skeletal muscle function article in journal of human genetics 6515. Pathway analysis with genomewide association study gwas. Cdkal1 rs7756992 and type 2 diabetes figure 2a presents the forest plot of risk allele or of an individual study and metaanalysis for association between cdkal1 rs7756992 and type 2 diabetes in a total of 22,839 type 2 diabetes patients and 31,429 control subjects from the 21 studies. Metaanalysis of genomewide association studies identifies.
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