Linkage of type 2 diabetes on chromosome 9p24 in Mexican Americans: Additional evidence from the Veterans Administration Genetic Epidemiology Study (VAGES)

Vidya S. Farook, Dawn K. Coletta, Sobha Puppala, Jennifer Schneider, Geetha Chittoor, Shirley L. Hu, Deidre A. Winnier, Luke Norton, Thomas D. Dyer, Rector Arya, Shelley A. Cole, Melanie Carless, Harald H. Göring, Laura Almasy, Michael C. Mahaney, Anthony G. Comuzzie, Joanne E. Curran, John Blangero, Ravindranath Duggirala, Donna M. LehmanChristopher P. Jenkinson, Ralph A. Defronzo

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective: Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage (GWL) analysis to localize T2DM susceptibility loci in Mexican Americans. Methods: We used the phenotypic and genotypic data from 1,122 Mexican-American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). GWL analysis was performed using the variance components approach. Data from 2 additional Mexican-American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results: After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, p = 2.7 × 10-6). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region also in SAFDGS, we found the significant and increased linkage evidence (LOD = 4.3, empirical p = 1.0 × 10-5, genome-wide p = 1.6 × 10-3) for T2DM at the same chromosomal region, when we performed a GWL analysis of the VAGES data combined with the SAFHS and SAFDGS data. Conclusion: Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies involving T2DM-related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes.

Original languageEnglish (US)
Pages (from-to)36-46
Number of pages11
JournalHuman Heredity
Volume76
Issue number1
DOIs
StatePublished - Oct 2013

Fingerprint

United States Department of Veterans Affairs
Molecular Epidemiology
Type 2 Diabetes Mellitus
Chromosomes
Gallbladder
Genome
Genome-Wide Association Study
Metabolic Diseases
Ethnic Groups
Genes

Keywords

  • Chromosome 9p24
  • Linkage
  • Mexican Americans
  • Type 2 diabetes
  • VAGES

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Linkage of type 2 diabetes on chromosome 9p24 in Mexican Americans : Additional evidence from the Veterans Administration Genetic Epidemiology Study (VAGES). / Farook, Vidya S.; Coletta, Dawn K.; Puppala, Sobha; Schneider, Jennifer; Chittoor, Geetha; Hu, Shirley L.; Winnier, Deidre A.; Norton, Luke; Dyer, Thomas D.; Arya, Rector; Cole, Shelley A.; Carless, Melanie; Göring, Harald H.; Almasy, Laura; Mahaney, Michael C.; Comuzzie, Anthony G.; Curran, Joanne E.; Blangero, John; Duggirala, Ravindranath; Lehman, Donna M.; Jenkinson, Christopher P.; Defronzo, Ralph A.

In: Human Heredity, Vol. 76, No. 1, 10.2013, p. 36-46.

Research output: Contribution to journalArticle

Farook, VS, Coletta, DK, Puppala, S, Schneider, J, Chittoor, G, Hu, SL, Winnier, DA, Norton, L, Dyer, TD, Arya, R, Cole, SA, Carless, M, Göring, HH, Almasy, L, Mahaney, MC, Comuzzie, AG, Curran, JE, Blangero, J, Duggirala, R, Lehman, DM, Jenkinson, CP & Defronzo, RA 2013, 'Linkage of type 2 diabetes on chromosome 9p24 in Mexican Americans: Additional evidence from the Veterans Administration Genetic Epidemiology Study (VAGES)', Human Heredity, vol. 76, no. 1, pp. 36-46. https://doi.org/10.1159/000354849
Farook, Vidya S. ; Coletta, Dawn K. ; Puppala, Sobha ; Schneider, Jennifer ; Chittoor, Geetha ; Hu, Shirley L. ; Winnier, Deidre A. ; Norton, Luke ; Dyer, Thomas D. ; Arya, Rector ; Cole, Shelley A. ; Carless, Melanie ; Göring, Harald H. ; Almasy, Laura ; Mahaney, Michael C. ; Comuzzie, Anthony G. ; Curran, Joanne E. ; Blangero, John ; Duggirala, Ravindranath ; Lehman, Donna M. ; Jenkinson, Christopher P. ; Defronzo, Ralph A. / Linkage of type 2 diabetes on chromosome 9p24 in Mexican Americans : Additional evidence from the Veterans Administration Genetic Epidemiology Study (VAGES). In: Human Heredity. 2013 ; Vol. 76, No. 1. pp. 36-46.
@article{112a3e5e4197458bb22a3f2a6e165113,
title = "Linkage of type 2 diabetes on chromosome 9p24 in Mexican Americans: Additional evidence from the Veterans Administration Genetic Epidemiology Study (VAGES)",
abstract = "Objective: Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage (GWL) analysis to localize T2DM susceptibility loci in Mexican Americans. Methods: We used the phenotypic and genotypic data from 1,122 Mexican-American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). GWL analysis was performed using the variance components approach. Data from 2 additional Mexican-American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results: After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, p = 2.7 × 10-6). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region also in SAFDGS, we found the significant and increased linkage evidence (LOD = 4.3, empirical p = 1.0 × 10-5, genome-wide p = 1.6 × 10-3) for T2DM at the same chromosomal region, when we performed a GWL analysis of the VAGES data combined with the SAFHS and SAFDGS data. Conclusion: Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies involving T2DM-related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes.",
keywords = "Chromosome 9p24, Linkage, Mexican Americans, Type 2 diabetes, VAGES",
author = "Farook, {Vidya S.} and Coletta, {Dawn K.} and Sobha Puppala and Jennifer Schneider and Geetha Chittoor and Hu, {Shirley L.} and Winnier, {Deidre A.} and Luke Norton and Dyer, {Thomas D.} and Rector Arya and Cole, {Shelley A.} and Melanie Carless and G{\"o}ring, {Harald H.} and Laura Almasy and Mahaney, {Michael C.} and Comuzzie, {Anthony G.} and Curran, {Joanne E.} and John Blangero and Ravindranath Duggirala and Lehman, {Donna M.} and Jenkinson, {Christopher P.} and Defronzo, {Ralph A.}",
year = "2013",
month = "10",
doi = "10.1159/000354849",
language = "English (US)",
volume = "76",
pages = "36--46",
journal = "Human Heredity",
issn = "0001-5652",
publisher = "S. Karger AG",
number = "1",

}

TY - JOUR

T1 - Linkage of type 2 diabetes on chromosome 9p24 in Mexican Americans

T2 - Additional evidence from the Veterans Administration Genetic Epidemiology Study (VAGES)

AU - Farook, Vidya S.

AU - Coletta, Dawn K.

AU - Puppala, Sobha

AU - Schneider, Jennifer

AU - Chittoor, Geetha

AU - Hu, Shirley L.

AU - Winnier, Deidre A.

AU - Norton, Luke

AU - Dyer, Thomas D.

AU - Arya, Rector

AU - Cole, Shelley A.

AU - Carless, Melanie

AU - Göring, Harald H.

AU - Almasy, Laura

AU - Mahaney, Michael C.

AU - Comuzzie, Anthony G.

AU - Curran, Joanne E.

AU - Blangero, John

AU - Duggirala, Ravindranath

AU - Lehman, Donna M.

AU - Jenkinson, Christopher P.

AU - Defronzo, Ralph A.

PY - 2013/10

Y1 - 2013/10

N2 - Objective: Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage (GWL) analysis to localize T2DM susceptibility loci in Mexican Americans. Methods: We used the phenotypic and genotypic data from 1,122 Mexican-American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). GWL analysis was performed using the variance components approach. Data from 2 additional Mexican-American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results: After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, p = 2.7 × 10-6). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region also in SAFDGS, we found the significant and increased linkage evidence (LOD = 4.3, empirical p = 1.0 × 10-5, genome-wide p = 1.6 × 10-3) for T2DM at the same chromosomal region, when we performed a GWL analysis of the VAGES data combined with the SAFHS and SAFDGS data. Conclusion: Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies involving T2DM-related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes.

AB - Objective: Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage (GWL) analysis to localize T2DM susceptibility loci in Mexican Americans. Methods: We used the phenotypic and genotypic data from 1,122 Mexican-American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). GWL analysis was performed using the variance components approach. Data from 2 additional Mexican-American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results: After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, p = 2.7 × 10-6). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region also in SAFDGS, we found the significant and increased linkage evidence (LOD = 4.3, empirical p = 1.0 × 10-5, genome-wide p = 1.6 × 10-3) for T2DM at the same chromosomal region, when we performed a GWL analysis of the VAGES data combined with the SAFHS and SAFDGS data. Conclusion: Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies involving T2DM-related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes.

KW - Chromosome 9p24

KW - Linkage

KW - Mexican Americans

KW - Type 2 diabetes

KW - VAGES

UR - http://www.scopus.com/inward/record.url?scp=84886792159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886792159&partnerID=8YFLogxK

U2 - 10.1159/000354849

DO - 10.1159/000354849

M3 - Article

C2 - 24060607

AN - SCOPUS:84886792159

VL - 76

SP - 36

EP - 46

JO - Human Heredity

JF - Human Heredity

SN - 0001-5652

IS - 1

ER -