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Linkage of Type 2 Diabetes Mellitus and of Age at Onset to a Genetic Location on Chromosome 10q in Mexican Americans
Open accessAbstract
Since little is known about chromosomal locations harboring type 2 diabetes-susceptibility genes, we conducted a genomewide scan for such genes in a Mexican American population. We used data from 27 low-income extended Mexican American pedigrees consisting of 440 individuals for whom genotypic data are available for 379 markers. We used a variance-components technique to conduct multipoint linkage analyses for two phenotypes: type 2 diabetes (a discrete trait) and age at onset of diabetes (a truncated quantitative trait). For the multipoint analyses, a subset of 295 markers was selected on the basis of optimal spacing and informativeness. We found significant evidence that a susceptibility locus near the marker D10S587 on chromosome 10q influences age at onset of diabetes (LOD score 3.75) and is also linked with type 2 diabetes itself (LOD score 2.88). This susceptibility locus explains 63.8%+/-9.9% (P=. 000016) of the total phenotypic variation in age at onset of diabetes and 65.7%+/-10.9% (P=.000135) of the total variation in liability to type 2 diabetes. Weaker evidence was found for linkage of diabetes and of age at onset to regions on chromosomes 3p, 4q, and 9p. In conclusion, our strongest evidence for linkage to both age at onset of diabetes and type 2 diabetes itself in the Mexican American population was for a region on chromosome 10q.
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“The first associated loci, in genes including TCF7L2, INSR, IRS1, GCK and KCNJ11 (refs.77,78), were originally identified by linkage or candidate gene studies, and since the turn of the century, increasing size and depth of genome-wide association studies have rapidly expanded the list of associated loci in type 2 diabetes to more than 250 with 400 independent signals79.”
From 100 years of insulin: celebrating the past, present and future of diabetes therapy (2021) · cites this paper as [77]
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Metadata
- Authors
- Duggirala, R., Blangero, J., Almasy, L., Dyer, T. D., Williams, K. L., Leach, R. J., O'Connell, P., & Stern, M. P.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Texas Biomedical Research Institute (US)
- Corresponding author
- Duggirala, Ravindranath
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 1999-04
- Volume
- 64
- Issue
- 4
- Pages
- 1127-1140
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1377837
- OpenAlex
- W2058805992
- Cited by
- 337
- References
- 70
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 8 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 12 · 2019: 8 · 2018: 9 · 2017: 4 · 2016: 11 · 2015: 17 · 2014: 14 · 2013: 11 · 2012: 7
- FWCI
- 11.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- World Health Organization
- National Institutes of Health (5r29dk044297-04)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-44297, R01DK042273, R01DK047482, DK47482, DK42273)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- type 2 diabetes, age at onset of diabetes, genetic susceptibility, chromosome 10q, genetic linkage, Mexican Americans, extended pedigrees, multipoint linkage analysis
- MeSH terms
- Age Factors, Chromosome Mapping, Chromosomes, Human, Pair 10, Diabetes Mellitus, Type 2, Female, Genotype, Hispanic or Latino, Humans, Lod Score, Male, Mexico, Pedigree, Sex Factors, United States, Age of Onset, Disease-Free Survival, Microsatellite Repeats, Quantitative Trait, Heritable, Penetrance, Genetic Predisposition to Disease
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