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Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort

OBJECTIVE—We used a single nucleotide polymorphism (SNP) map in a large cohort of 580 African American families to identify regions linked to type 2 diabetes, age of type 2 diabetes diagnosis, and BMI. RESEARCH DESIGN AND METHODS—After removing outliers and problematic samples, we conducted linkage...

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Autores principales: Elbein, Steven C., Das, Swapan K., Hallman, D. Michael, Hanis, Craig L., Hasstedt, Sandra J.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606884/
https://www.ncbi.nlm.nih.gov/pubmed/18840782
http://dx.doi.org/10.2337/db08-0931
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author Elbein, Steven C.
Das, Swapan K.
Hallman, D. Michael
Hanis, Craig L.
Hasstedt, Sandra J.
author_facet Elbein, Steven C.
Das, Swapan K.
Hallman, D. Michael
Hanis, Craig L.
Hasstedt, Sandra J.
author_sort Elbein, Steven C.
collection PubMed
description OBJECTIVE—We used a single nucleotide polymorphism (SNP) map in a large cohort of 580 African American families to identify regions linked to type 2 diabetes, age of type 2 diabetes diagnosis, and BMI. RESEARCH DESIGN AND METHODS—After removing outliers and problematic samples, we conducted linkage analysis using 5,914 SNPs in 1,344 individuals from 530 families. Linkage analysis was conducted using variance components for type 2 diabetes, age of type 2 diabetes diagnosis, and BMI and nonparametric linkage analyses. Ordered subset analyses were conducted ranking on age of type 2 diabetes diagnosis, BMI, waist circumference, waist-to-hip ratio, and amount of European admixture. Admixture mapping was conducted using 4,486 markers not in linkage disequilibrium. RESULTS—The strongest signal for type 2 diabetes (logarithm of odds [LOD] 4.53) was a broad peak on chromosome 2, with weaker linkage to age of type 2 diabetes diagnosis (LOD 1.82). Type 2 diabetes and age of type 2 diabetes diagnosis were linked to chromosome 13p (3–22 cM; LOD 2.42 and 2.46, respectively). Age of type 2 diabetes diagnosis was linked to 18p (66 cM; LOD 2.96). We replicated previous reports on chromosome 7p (79 cM; LOD 2.93). Ordered subset analysis did not overlap with linkage of unselected families. The best admixture score was on chromosome 12 (90 cM; P = 0.0003). CONCLUSIONS—The linkage regions on chromosomes 7 (27–78 cM) and 18p overlap prior reports, whereas regions on 2p and 13p linkage are novel. Among potential candidate genes implicated are TCF7L1, VAMP5, VAMP8, CDK8, INSIG2, IPF1, PAX8, IL18R1, members of the IL1 and IL1 receptor families, and MAP4K4. These studies provide a complementary approach to genome-wide association scans to identify causative genes for African American diabetes.
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spelling pubmed-26068842010-01-01 Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort Elbein, Steven C. Das, Swapan K. Hallman, D. Michael Hanis, Craig L. Hasstedt, Sandra J. Diabetes Genetics OBJECTIVE—We used a single nucleotide polymorphism (SNP) map in a large cohort of 580 African American families to identify regions linked to type 2 diabetes, age of type 2 diabetes diagnosis, and BMI. RESEARCH DESIGN AND METHODS—After removing outliers and problematic samples, we conducted linkage analysis using 5,914 SNPs in 1,344 individuals from 530 families. Linkage analysis was conducted using variance components for type 2 diabetes, age of type 2 diabetes diagnosis, and BMI and nonparametric linkage analyses. Ordered subset analyses were conducted ranking on age of type 2 diabetes diagnosis, BMI, waist circumference, waist-to-hip ratio, and amount of European admixture. Admixture mapping was conducted using 4,486 markers not in linkage disequilibrium. RESULTS—The strongest signal for type 2 diabetes (logarithm of odds [LOD] 4.53) was a broad peak on chromosome 2, with weaker linkage to age of type 2 diabetes diagnosis (LOD 1.82). Type 2 diabetes and age of type 2 diabetes diagnosis were linked to chromosome 13p (3–22 cM; LOD 2.42 and 2.46, respectively). Age of type 2 diabetes diagnosis was linked to 18p (66 cM; LOD 2.96). We replicated previous reports on chromosome 7p (79 cM; LOD 2.93). Ordered subset analysis did not overlap with linkage of unselected families. The best admixture score was on chromosome 12 (90 cM; P = 0.0003). CONCLUSIONS—The linkage regions on chromosomes 7 (27–78 cM) and 18p overlap prior reports, whereas regions on 2p and 13p linkage are novel. Among potential candidate genes implicated are TCF7L1, VAMP5, VAMP8, CDK8, INSIG2, IPF1, PAX8, IL18R1, members of the IL1 and IL1 receptor families, and MAP4K4. These studies provide a complementary approach to genome-wide association scans to identify causative genes for African American diabetes. American Diabetes Association 2009-01 /pmc/articles/PMC2606884/ /pubmed/18840782 http://dx.doi.org/10.2337/db08-0931 Text en Copyright © 2009, American Diabetes Association Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Genetics
Elbein, Steven C.
Das, Swapan K.
Hallman, D. Michael
Hanis, Craig L.
Hasstedt, Sandra J.
Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort
title Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort
title_full Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort
title_fullStr Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort
title_full_unstemmed Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort
title_short Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort
title_sort genome-wide linkage and admixture mapping of type 2 diabetes in african american families from the american diabetes association gennid (genetics of niddm) study cohort
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606884/
https://www.ncbi.nlm.nih.gov/pubmed/18840782
http://dx.doi.org/10.2337/db08-0931
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