Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations - Significant evidence for linkage on chromosome 4q in African Americans

The family investigation of nephropathy and diabetes research group

Alka Malhotra, Robert P. Igo, Farook Thameem, W. H Linda Kao, Hanna E. Abboud, Sharon G. Adler, Nedal H. Arar, Donald W. Bowden, Ravindranath Duggirala, Barry I. Freedman, Katrina A B Goddard, Eli Ipp, Sudha K. Iyengar, Paul L. Kimmel, William C. Knowler, Orly Kohn, David Leehey, Lucy Ann Meoni, Robert G. Nelson, Susanne B. Nicholas & 13 others Rulan S. Parekh, Stephen S. Rich, Yii Der I Chen, Mohammed F. Saad, Marina Scavini, Jeffrey R. Schelling, John R. Sedor, Vallabh O. Shah, Kent D. Taylor, Denyse Thornley-Brown, Philip G. Zager, Amanda Horvath, Robert L. Hanson

Research output: Contribution to journalArticle

Abstract

Background: Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Methods: Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Results: Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD =. 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD >1.71 have been identified in previously published studies. Conclusions: The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.

Original languageEnglish (US)
Pages (from-to)740-747
Number of pages8
JournalDiabetes/Metabolism Research and Reviews
Volume25
Issue number8
DOIs
StatePublished - Nov 2009

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African Americans
Type 2 Diabetes Mellitus
Chromosomes
Genome
Research
Population
Ethnic Groups
North American Indians
Single Nucleotide Polymorphism
Genes

Keywords

  • Ethnicity
  • FIND
  • Linkage analysis
  • Type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations - Significant evidence for linkage on chromosome 4q in African Americans : The family investigation of nephropathy and diabetes research group. / Malhotra, Alka; Igo, Robert P.; Thameem, Farook; Kao, W. H Linda; Abboud, Hanna E.; Adler, Sharon G.; Arar, Nedal H.; Bowden, Donald W.; Duggirala, Ravindranath; Freedman, Barry I.; Goddard, Katrina A B; Ipp, Eli; Iyengar, Sudha K.; Kimmel, Paul L.; Knowler, William C.; Kohn, Orly; Leehey, David; Meoni, Lucy Ann; Nelson, Robert G.; Nicholas, Susanne B.; Parekh, Rulan S.; Rich, Stephen S.; Chen, Yii Der I; Saad, Mohammed F.; Scavini, Marina; Schelling, Jeffrey R.; Sedor, John R.; Shah, Vallabh O.; Taylor, Kent D.; Thornley-Brown, Denyse; Zager, Philip G.; Horvath, Amanda; Hanson, Robert L.

In: Diabetes/Metabolism Research and Reviews, Vol. 25, No. 8, 11.2009, p. 740-747.

Research output: Contribution to journalArticle

Malhotra, A, Igo, RP, Thameem, F, Kao, WHL, Abboud, HE, Adler, SG, Arar, NH, Bowden, DW, Duggirala, R, Freedman, BI, Goddard, KAB, Ipp, E, Iyengar, SK, Kimmel, PL, Knowler, WC, Kohn, O, Leehey, D, Meoni, LA, Nelson, RG, Nicholas, SB, Parekh, RS, Rich, SS, Chen, YDI, Saad, MF, Scavini, M, Schelling, JR, Sedor, JR, Shah, VO, Taylor, KD, Thornley-Brown, D, Zager, PG, Horvath, A & Hanson, RL 2009, 'Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations - Significant evidence for linkage on chromosome 4q in African Americans: The family investigation of nephropathy and diabetes research group', Diabetes/Metabolism Research and Reviews, vol. 25, no. 8, pp. 740-747. https://doi.org/10.1002/dmrr.1031
Malhotra, Alka ; Igo, Robert P. ; Thameem, Farook ; Kao, W. H Linda ; Abboud, Hanna E. ; Adler, Sharon G. ; Arar, Nedal H. ; Bowden, Donald W. ; Duggirala, Ravindranath ; Freedman, Barry I. ; Goddard, Katrina A B ; Ipp, Eli ; Iyengar, Sudha K. ; Kimmel, Paul L. ; Knowler, William C. ; Kohn, Orly ; Leehey, David ; Meoni, Lucy Ann ; Nelson, Robert G. ; Nicholas, Susanne B. ; Parekh, Rulan S. ; Rich, Stephen S. ; Chen, Yii Der I ; Saad, Mohammed F. ; Scavini, Marina ; Schelling, Jeffrey R. ; Sedor, John R. ; Shah, Vallabh O. ; Taylor, Kent D. ; Thornley-Brown, Denyse ; Zager, Philip G. ; Horvath, Amanda ; Hanson, Robert L. / Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations - Significant evidence for linkage on chromosome 4q in African Americans : The family investigation of nephropathy and diabetes research group. In: Diabetes/Metabolism Research and Reviews. 2009 ; Vol. 25, No. 8. pp. 740-747.
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title = "Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations - Significant evidence for linkage on chromosome 4q in African Americans: The family investigation of nephropathy and diabetes research group",
abstract = "Background: Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Methods: Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Results: Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD =. 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD >1.71 have been identified in previously published studies. Conclusions: The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.",
keywords = "Ethnicity, FIND, Linkage analysis, Type 2 diabetes",
author = "Alka Malhotra and Igo, {Robert P.} and Farook Thameem and Kao, {W. H Linda} and Abboud, {Hanna E.} and Adler, {Sharon G.} and Arar, {Nedal H.} and Bowden, {Donald W.} and Ravindranath Duggirala and Freedman, {Barry I.} and Goddard, {Katrina A B} and Eli Ipp and Iyengar, {Sudha K.} and Kimmel, {Paul L.} and Knowler, {William C.} and Orly Kohn and David Leehey and Meoni, {Lucy Ann} and Nelson, {Robert G.} and Nicholas, {Susanne B.} and Parekh, {Rulan S.} and Rich, {Stephen S.} and Chen, {Yii Der I} and Saad, {Mohammed F.} and Marina Scavini and Schelling, {Jeffrey R.} and Sedor, {John R.} and Shah, {Vallabh O.} and Taylor, {Kent D.} and Denyse Thornley-Brown and Zager, {Philip G.} and Amanda Horvath and Hanson, {Robert L.}",
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TY - JOUR

T1 - Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations - Significant evidence for linkage on chromosome 4q in African Americans

T2 - The family investigation of nephropathy and diabetes research group

AU - Malhotra, Alka

AU - Igo, Robert P.

AU - Thameem, Farook

AU - Kao, W. H Linda

AU - Abboud, Hanna E.

AU - Adler, Sharon G.

AU - Arar, Nedal H.

AU - Bowden, Donald W.

AU - Duggirala, Ravindranath

AU - Freedman, Barry I.

AU - Goddard, Katrina A B

AU - Ipp, Eli

AU - Iyengar, Sudha K.

AU - Kimmel, Paul L.

AU - Knowler, William C.

AU - Kohn, Orly

AU - Leehey, David

AU - Meoni, Lucy Ann

AU - Nelson, Robert G.

AU - Nicholas, Susanne B.

AU - Parekh, Rulan S.

AU - Rich, Stephen S.

AU - Chen, Yii Der I

AU - Saad, Mohammed F.

AU - Scavini, Marina

AU - Schelling, Jeffrey R.

AU - Sedor, John R.

AU - Shah, Vallabh O.

AU - Taylor, Kent D.

AU - Thornley-Brown, Denyse

AU - Zager, Philip G.

AU - Horvath, Amanda

AU - Hanson, Robert L.

PY - 2009/11

Y1 - 2009/11

N2 - Background: Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Methods: Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Results: Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD =. 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD >1.71 have been identified in previously published studies. Conclusions: The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.

AB - Background: Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Methods: Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Results: Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD =. 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD >1.71 have been identified in previously published studies. Conclusions: The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.

KW - Ethnicity

KW - FIND

KW - Linkage analysis

KW - Type 2 diabetes

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