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Cited by 338Genetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and AnimalsDiabetes and associated disorders

Linkage of Type 2 Diabetes Mellitus and of Age at Onset to a Genetic Location on Chromosome 10q in Mexican Americans

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Duggirala, Ravindranath, Blangero, John, Almasy, Laura, Dyer, Thomas D., Williams, Kenneth L., Leach, Robin J., O'Connell, Peter, Stern, Michael P.·1999·The American Journal of Human Genetics
DOI 10.1086/302316PMC PMC1377837
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Abstract

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 type 2 diabetes loci, in genes including TCF7L2, INSR, IRS1, GCK and KCNJ11, were originally identified by linkage or candidate gene studies.

    “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]

    The Abstract (page unavailable) reports that the authors used linkage analysis to identify a type 2 diabetes susceptibility region on chromosome 10q in Mexican Americans. That supports linkage as an early discovery approach, but the paper does not identify associated loci in TCF7L2, INSR, IRS1, GCK, or KCNJ11, or establish how those named loci were first identified. (LLM, conf=0.87)

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Research works printed but not linked: 5

  1. [2]2. Almasy, L ∙ Dyer, TD ∙ Blangero, J Bivariate quantitative trait linkage analysis: pleiotropy versus co-incident linkages Genet Epidemiol. 1997; 14:953-958 Crossref Scopus (300) PubMed Google Scholar
  2. [6]6. Blangero, J ∙ Almasy, L Multipoint oligogenic linkage analysis of quantitative traits Genet Epidemiol. 1997; 14:959-964 Crossref Scopus (181) PubMed Google Scholar
  3. [16]16. Duggirala, R ∙ Williams, JT ∙ Williams-Blangero, S ... A variance component approach to dichotomous trait linkage analysis using a threshold model Genet Epidemiol. 1997; 14:987-992 Crossref Scopus (159) PubMed Google Scholar
  4. [23]23. Fasman, KH ∙ Cuticchia, AJ ∙ Kingsbury, DT The GDB™ human genome data base Nucleic Acids Res. 1994; 22:3462-3469 Crossref Scopus (70) PubMed Google Scholar
  5. [30]30. Greenberg, DA ∙ Hodge, SE ∙ Vieland, VJ ... Reply to Farrall Am J Hum Genet. 1997; 60:738 PubMed Google Scholar

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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)
DOI
10.1086/302316
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
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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