Genetic analysis of type II diabetes in Finnish population
芬兰人群II型糖尿病的遗传分析
基本信息
- 批准号:7968834
- 负责人:
- 金额:$ 223.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:AdultAllelesAlternative SplicingAutomobile DrivingBiochemicalBiological AssayBlood PressureCell Culture TechniquesCessation of lifeChromatin StructureChronic DiseaseCollectionDataDiabetes MellitusDiagnosisDietDiseaseEnvironmental Risk FactorFamilyFinlandGene ExpressionGenetic Predisposition to DiseaseGenotypeHaplotypesHeightHigh Density Lipoprotein CholesterolHuman Genome ProjectIndividualInheritedInvestigationLaboratoriesLow-Density LipoproteinsMorbidity - disease rateNightmareNon-Insulin-Dependent Diabetes MellitusObesityPhenotypePlayPopulationPreventionRiskRoleSamplingTCF7L2 geneTechnologyTriglyceridesUnited StatesVariantWorkbasediabetes mellitus geneticsdiabeticdisorder riskfasting glucosegenetic analysisgenetic linkagegenome wide association studygenome-widemortalitytrait
项目摘要
Type 2 diabetes (T2D) is one of the major causes of morbidity and mortality in the developed world. While environmental factors such as diet play a significant role, familial clustering indicates that there must be significant genetic susceptibility factors at work. For fifteen years we have been engaged in a large collaborative study entitled FUSION (Finland - United States Investigation of NIDDM), in which more than 10,000 individuals with diabetes (and suitable controls) from Finland are being studied, using careful phenotyping of diabetes and diabetes-associated quantitative traits, and genome-wide genetic linkage and association. Large numbers of additional samples are also now available from several collaborators around the world. We have developed and applied new high throughput genotyping approaches in the laboratory, which have allowed the collection of a massive amount of data from these Finnish diabetics and their families. Using the genome wide association study (GWAS) approach, we have now contributed to the identification of no less than 32 loci for T2D, and have identified additional loci harboring variants that have important effects on obesity, fasting glucose, LDL and HDL cholesterol, triglycerides, blood pressure, and adult height. We are now investigating the functional basis of disease risk that arises from several of these variants, including those in TCF7L2, SLC30A8, CDKN2A/B, IGF2BP2, HMGCR and GCKR. This analysis includes high throughput sequencing of these loci to identify common and rare alleles that may be driving the association, analysis of the relationship between gene expression, alternative splicing, chromatin structure, and risk haplotypes, and cell culture and biochemical assays. With this kind of substantial progress, we are confident that the geneticist's nightmare (Jim Neel's description of the genetics of diabetes) is coming to an end.
2 型糖尿病 (T2D) 是发达国家发病和死亡的主要原因之一。虽然饮食等环境因素起着重要作用,但家族聚集表明一定有显着的遗传易感性因素在起作用。十五年来,我们一直致力于一项名为 FUSION(芬兰 - 美国 NIDDM 调查)的大型合作研究,其中正在对来自芬兰的 10,000 多名糖尿病患者(和合适的对照)进行研究,使用糖尿病和糖尿病相关数量性状的仔细表型分析以及全基因组遗传连锁和关联。现在还可以从世界各地的几个合作者那里获得大量额外的样本。我们在实验室开发并应用了新的高通量基因分型方法,从而可以从这些芬兰糖尿病患者及其家人那里收集大量数据。利用全基因组关联研究 (GWAS) 方法,我们现已鉴定出不少于 32 个 T2D 基因座,并鉴定出其他含有变异的基因座,这些变异对肥胖、空腹血糖、低密度脂蛋白和高密度脂蛋白胆固醇、甘油三酯、血压和成人身高有重要影响。我们现在正在研究其中几种变异引起的疾病风险的功能基础,包括 TCF7L2、SLC30A8、CDKN2A/B、IGF2BP2、HMGCR 和 GCKR 中的变异。该分析包括对这些基因座进行高通量测序,以识别可能驱动关联的常见和罕见等位基因,分析基因表达、选择性剪接、染色质结构和风险单倍型之间的关系,以及细胞培养和生化测定。随着这种实质性进展,我们相信遗传学家的噩梦(吉姆·尼尔对糖尿病遗传学的描述)即将结束。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Lawrence C Brody其他文献
Excess folic acid exposure increases uracil misincorporation into DNA in a tissue-specific manner in a mouse model of reduced methionine synthase expression
在甲硫氨酸合酶表达减少的小鼠模型中,过量叶酸暴露会以组织特异性方式增加尿嘧啶错掺入 DNA
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Katarina E. Heyden;Olga V. Malysheva;Amanda J. MacFarlane;Lawrence C Brody;M. Field - 通讯作者:
M. Field
Lawrence C Brody的其他文献
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{{ truncateString('Lawrence C Brody', 18)}}的其他基金
Folate and vitamin B12 metabolism in neural tube defects
神经管缺陷中的叶酸和维生素 B12 代谢
- 批准号:
6430092 - 财政年份:
- 资助金额:
$ 223.75万 - 项目类别:
BRCA1 and BRCA2 gene in breast cancer pathogenesis
BRCA1和BRCA2基因在乳腺癌发病机制中的作用
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6988627 - 财政年份:
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$ 223.75万 - 项目类别:
Gene-environment interactions in asthma in mice and humans
小鼠和人类哮喘中基因与环境的相互作用
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7968946 - 财政年份:
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$ 223.75万 - 项目类别:
The contribution folate and vitamin B12 genes to disease.
叶酸和维生素 B12 基因对疾病的贡献。
- 批准号:
8565529 - 财政年份:
- 资助金额:
$ 223.75万 - 项目类别:
The role of the BRCA1 and BRCA2 gene in the pathogenesis
BRCA1和BRCA2基因在发病机制中的作用
- 批准号:
7315995 - 财政年份:
- 资助金额:
$ 223.75万 - 项目类别:
The contribution folate and vitamin B12 genes to disease.
叶酸和维生素 B12 基因对疾病的贡献。
- 批准号:
10700697 - 财政年份:
- 资助金额:
$ 223.75万 - 项目类别:
The genetics of folate and vitamin B12 metabolism relate
叶酸和维生素 B12 代谢的遗传学相关
- 批准号:
7147954 - 财政年份:
- 资助金额:
$ 223.75万 - 项目类别:
ANALYSIS OF COMMON CANCER ASSOCIATED MUTATIONS IN ASHKENAZI JEWS
德系犹太人常见癌症相关突变分析
- 批准号:
6109025 - 财政年份:
- 资助金额:
$ 223.75万 - 项目类别:
The genetics of folate and vitamin B12 metabolism relate
叶酸和维生素 B12 代谢的遗传学相关
- 批准号:
6988747 - 财政年份:
- 资助金额:
$ 223.75万 - 项目类别:
The role of the BRCA1 and BRCA2 gene in the pathogenesis
BRCA1和BRCA2基因在发病机制中的作用
- 批准号:
6830360 - 财政年份:
- 资助金额:
$ 223.75万 - 项目类别:
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