Genetic Analysis of Type II Diabetes in Finnish Population

Collins, Francis S.

Abstract

We have completed a genome scan for type 2 diabetes and related phenotypes at an average resolution of 10cM on 2401 individuals. In all, more than 1.3 million genotypes have been generated with an overall error rate of 0.11 percent. The maximum multipoint weighted lod score for diabetes is 2.15 on chromosome 20 at 69.5 cM from the most p telomeric marker. Additional multipoint lod scores of 1.99 at 17.5 cM and 1.90 at 51.5 cM are also seen on this chromosome. The HNF4alpha gene (MODY1, approximately 65 cM) has been excluded as a major contributor to the maximum lod score. Only one other region, that on chromosome 11, has a multipoint weighted lod score greater than 1 (1.18 at 79.5 cM). Stratification analysis based on a diabetes-related phenotype gives significant linkage results (p<0.05) for diabetes on chromosomes 10, 14 and 22. We have also received, diluted and organized 2916 DNA samples from extended family members and from a new replication sample. Association analyses at an average resolution of 2 cM will be conducted on chromosome 20 using the information in the combined dataset according to birthplaces of parents or grandparents in Finland. We then plan to pursue positional cloning of diabetes-related genes on chromosome 20 after narrowing down areas of linkage to manageable intervals.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Human Genome Research Institute (NHGRI)
• Type: Intramural Research (Z01)
• Project #: 1Z01HG000024-04
• Application #: 6108955
• Study Section: Special Emphasis Panel (GMBB)
• Support Year: 4
• Fiscal Year: 1998

Institution

• Name: National Human Genome Research Institute
• Country: United States

Publications

Teslovich, Tanya M; Kim, Daniel Seung; Yin, Xianyong et al. (2018) Identification of seven novel loci associated with amino acid levels using single-variant and gene-based tests in 8545 Finnish men from the METSIM study. Hum Mol Genet 27:1664-1674

Pan, David Z; Garske, Kristina M; Alvarez, Marcus et al. (2018) Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS. Nat Commun 9:1512

Latva-Rasku, Aino; Honka, Miikka-Juhani; Stan?áková, Alena et al. (2018) A Partial Loss-of-Function Variant in AKT2 Is Associated With Reduced Insulin-Mediated Glucose Uptake in Multiple Insulin-Sensitive Tissues: A Genotype-Based Callback Positron Emission Tomography Study. Diabetes 67:334-342

Justice, Anne E (see original citation for additional authors) (2017) Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun 8:14977

Wood, Andrew R; Jonsson, Anna; Jackson, Anne U et al. (2017) A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants. Diabetes 66:2296-2309

Manning, Alisa (see original citation for additional authors) (2017) A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk. Diabetes 66:2019-2032

Roman, Tamara S; Cannon, Maren E; Vadlamudi, Swarooparani et al. (2017) A Type 2 Diabetes-Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the ADCY5 Locus. Diabetes 66:2521-2530

Johnson, Amy R; Qin, Yuanyuan; Cozzo, Alyssa J et al. (2016) Metabolic reprogramming through fatty acid transport protein 1 (FATP1) regulates macrophage inflammatory potential and adipose inflammation. Mol Metab 5:506-526

Ehret, Georg B (see original citation for additional authors) (2016) The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat Genet 48:1171-1184

Surendran, Praveen (see original citation for additional authors) (2016) Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nat Genet 48:1151-1161