Meta-analysis of genome-wide linkage studies of quantitative lipid traits in families ascertained for type 2 diabetes

Alka Malhotra; Steven C. Elbein; Maggie C.Y. Ng; Ravindranath Duggirala; Rector Arya; Giuseppina Imperatore; Adebowale Adeyemo; Toni I. Pollin; Wen Chi Hsueh; Juliana C.N. Chan; Charles Rotimi; Robert L. Hanson; Sandra J. Hasstedt; Johanna K. Wolford; Eric Boerwinkle; John Buse; Ralph DeFronzo; David Ehrmann; Wilfred Fujimoto; Steven E. Kahn; Craig L. Hanis; Richard A. Mulivor; Jeanne C. Beck; Jill Norris; M. Alan Permutt; Philip Behn; Leslie Raffel; David C. Robbins

doi:10.2337/db06-1057

Meta-analysis of genome-wide linkage studies of quantitative lipid traits in families ascertained for type 2 diabetes

Alka Malhotra, Steven C. Elbein, Maggie C.Y. Ng, Ravindranath Duggirala, Rector Arya, Giuseppina Imperatore, Adebowale Adeyemo, Toni I. Pollin, Wen Chi Hsueh, Juliana C.N. Chan, Charles Rotimi, Robert L. Hanson, Sandra J. Hasstedt, Johanna K. Wolford, Eric Boerwinkle, John Buse, Ralph DeFronzo, David Ehrmann, Wilfred Fujimoto, Steven E. KahnCraig L. Hanis, Richard A. Mulivor, Jeanne C. Beck, Jill Norris, M. Alan Permutt, Philip Behn, Leslie Raffel, David C. Robbins

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Abstract

Dyslipidemia is a major risk factor for coronary heart disease, which is the predominant cause of mortality in individuals with type 2 diabetes. To date, nine linkage studies for quantitative lipid traits have been performed in families ascertained for type 2 diabetes, individually yielding linkage results that were largely nonoverlapping. Discrepancies in linkage findings are not uncommon and are typically due to limited sample size and heterogeneity. To address these issues and increase the power to detect linkage, we performed a meta-analysis of all published genome scans for quantitative lipid traits conducted in families ascertained for type 2 diabetes. Statistically significant evidence (i.e., P < 0.00043) for linkage was observed for total cholesterol on 7q32.3-q36.3 (152.43-182 cM; P = 0.00004), 19p13.3-p12 (6.57-38.05 cM; P = 0.00026), 19p12-q13.13 (38.05-69.53 cM; P = 0.00001), and 19q13.13-q13.43 (69.53-101.1 cM; P = 0.00033), as well as LDL on 19p13.3-p12 (P = 0.00041). Suggestive evidence (i.e., P < 0.00860) for linkage was also observed for LDL on 19p12-q13.13, triglycerides on 7p11-q21.11 (63.72-93.29 cM), triglyceride/HDL on 7p11-q21.11 and 19p12-q13.13, and LDL/HDL on 16q11.2-q24.3 (65.2-130.4 cM) and 19p12-q13.13. Linkage for lipid traits has been previously observed on both chromosomes 7 and 19 in several unrelated studies and, together with the results of this meta-analysis, provide compelling evidence that these regions harbor important determinants of lipid levels in individuals with type 2 diabetes.

Original language	English (US)
Pages (from-to)	890-896
Number of pages	7
Journal	Diabetes
Volume	56
Issue number	3
DOIs	https://doi.org/10.2337/db06-1057
State	Published - Mar 2007

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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Malhotra, A., Elbein, S. C., Ng, M. C. Y., Duggirala, R., Arya, R., Imperatore, G., Adeyemo, A., Pollin, T. I., Hsueh, W. C., Chan, J. C. N., Rotimi, C., Hanson, R. L., Hasstedt, S. J., Wolford, J. K., Boerwinkle, E., Buse, J., DeFronzo, R., Ehrmann, D., Fujimoto, W., ... Robbins, D. C. (2007). Meta-analysis of genome-wide linkage studies of quantitative lipid traits in families ascertained for type 2 diabetes. Diabetes, 56(3), 890-896. https://doi.org/10.2337/db06-1057

Malhotra, A, Elbein, SC, Ng, MCY, Duggirala, R, Arya, R, Imperatore, G, Adeyemo, A, Pollin, TI, Hsueh, WC, Chan, JCN, Rotimi, C, Hanson, RL, Hasstedt, SJ, Wolford, JK, Boerwinkle, E, Buse, J, DeFronzo, R, Ehrmann, D, Fujimoto, W, Kahn, SE, Hanis, CL, Mulivor, RA, Beck, JC, Norris, J, Permutt, MA, Behn, P, Raffel, L & Robbins, DC 2007, 'Meta-analysis of genome-wide linkage studies of quantitative lipid traits in families ascertained for type 2 diabetes', Diabetes, vol. 56, no. 3, pp. 890-896. https://doi.org/10.2337/db06-1057

@article{f09f5e213455423482bc661196bb664e,

title = "Meta-analysis of genome-wide linkage studies of quantitative lipid traits in families ascertained for type 2 diabetes",

abstract = "Dyslipidemia is a major risk factor for coronary heart disease, which is the predominant cause of mortality in individuals with type 2 diabetes. To date, nine linkage studies for quantitative lipid traits have been performed in families ascertained for type 2 diabetes, individually yielding linkage results that were largely nonoverlapping. Discrepancies in linkage findings are not uncommon and are typically due to limited sample size and heterogeneity. To address these issues and increase the power to detect linkage, we performed a meta-analysis of all published genome scans for quantitative lipid traits conducted in families ascertained for type 2 diabetes. Statistically significant evidence (i.e., P < 0.00043) for linkage was observed for total cholesterol on 7q32.3-q36.3 (152.43-182 cM; P = 0.00004), 19p13.3-p12 (6.57-38.05 cM; P = 0.00026), 19p12-q13.13 (38.05-69.53 cM; P = 0.00001), and 19q13.13-q13.43 (69.53-101.1 cM; P = 0.00033), as well as LDL on 19p13.3-p12 (P = 0.00041). Suggestive evidence (i.e., P < 0.00860) for linkage was also observed for LDL on 19p12-q13.13, triglycerides on 7p11-q21.11 (63.72-93.29 cM), triglyceride/HDL on 7p11-q21.11 and 19p12-q13.13, and LDL/HDL on 16q11.2-q24.3 (65.2-130.4 cM) and 19p12-q13.13. Linkage for lipid traits has been previously observed on both chromosomes 7 and 19 in several unrelated studies and, together with the results of this meta-analysis, provide compelling evidence that these regions harbor important determinants of lipid levels in individuals with type 2 diabetes.",

author = "Alka Malhotra and Elbein, {Steven C.} and Ng, {Maggie C.Y.} and Ravindranath Duggirala and Rector Arya and Giuseppina Imperatore and Adebowale Adeyemo and Pollin, {Toni I.} and Hsueh, {Wen Chi} and Chan, {Juliana C.N.} and Charles Rotimi and Hanson, {Robert L.} and Hasstedt, {Sandra J.} and Wolford, {Johanna K.} and Eric Boerwinkle and John Buse and Ralph DeFronzo and David Ehrmann and Wilfred Fujimoto and Kahn, {Steven E.} and Hanis, {Craig L.} and Mulivor, {Richard A.} and Beck, {Jeanne C.} and Jill Norris and Permutt, {M. Alan} and Philip Behn and Leslie Raffel and Robbins, {David C.}",

year = "2007",

month = mar,

doi = "10.2337/db06-1057",

language = "English (US)",

volume = "56",

pages = "890--896",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "3",

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T1 - Meta-analysis of genome-wide linkage studies of quantitative lipid traits in families ascertained for type 2 diabetes

AU - Malhotra, Alka

AU - Elbein, Steven C.

AU - Ng, Maggie C.Y.

AU - Duggirala, Ravindranath

AU - Arya, Rector

AU - Imperatore, Giuseppina

AU - Adeyemo, Adebowale

AU - Pollin, Toni I.

AU - Hsueh, Wen Chi

AU - Chan, Juliana C.N.

AU - Rotimi, Charles

AU - Hanson, Robert L.

AU - Hasstedt, Sandra J.

AU - Wolford, Johanna K.

AU - Boerwinkle, Eric

AU - Buse, John

AU - DeFronzo, Ralph

AU - Ehrmann, David

AU - Fujimoto, Wilfred

AU - Kahn, Steven E.

AU - Hanis, Craig L.

AU - Mulivor, Richard A.

AU - Beck, Jeanne C.

AU - Norris, Jill

AU - Permutt, M. Alan

AU - Behn, Philip

AU - Raffel, Leslie

AU - Robbins, David C.

PY - 2007/3

Y1 - 2007/3

N2 - Dyslipidemia is a major risk factor for coronary heart disease, which is the predominant cause of mortality in individuals with type 2 diabetes. To date, nine linkage studies for quantitative lipid traits have been performed in families ascertained for type 2 diabetes, individually yielding linkage results that were largely nonoverlapping. Discrepancies in linkage findings are not uncommon and are typically due to limited sample size and heterogeneity. To address these issues and increase the power to detect linkage, we performed a meta-analysis of all published genome scans for quantitative lipid traits conducted in families ascertained for type 2 diabetes. Statistically significant evidence (i.e., P < 0.00043) for linkage was observed for total cholesterol on 7q32.3-q36.3 (152.43-182 cM; P = 0.00004), 19p13.3-p12 (6.57-38.05 cM; P = 0.00026), 19p12-q13.13 (38.05-69.53 cM; P = 0.00001), and 19q13.13-q13.43 (69.53-101.1 cM; P = 0.00033), as well as LDL on 19p13.3-p12 (P = 0.00041). Suggestive evidence (i.e., P < 0.00860) for linkage was also observed for LDL on 19p12-q13.13, triglycerides on 7p11-q21.11 (63.72-93.29 cM), triglyceride/HDL on 7p11-q21.11 and 19p12-q13.13, and LDL/HDL on 16q11.2-q24.3 (65.2-130.4 cM) and 19p12-q13.13. Linkage for lipid traits has been previously observed on both chromosomes 7 and 19 in several unrelated studies and, together with the results of this meta-analysis, provide compelling evidence that these regions harbor important determinants of lipid levels in individuals with type 2 diabetes.

AB - Dyslipidemia is a major risk factor for coronary heart disease, which is the predominant cause of mortality in individuals with type 2 diabetes. To date, nine linkage studies for quantitative lipid traits have been performed in families ascertained for type 2 diabetes, individually yielding linkage results that were largely nonoverlapping. Discrepancies in linkage findings are not uncommon and are typically due to limited sample size and heterogeneity. To address these issues and increase the power to detect linkage, we performed a meta-analysis of all published genome scans for quantitative lipid traits conducted in families ascertained for type 2 diabetes. Statistically significant evidence (i.e., P < 0.00043) for linkage was observed for total cholesterol on 7q32.3-q36.3 (152.43-182 cM; P = 0.00004), 19p13.3-p12 (6.57-38.05 cM; P = 0.00026), 19p12-q13.13 (38.05-69.53 cM; P = 0.00001), and 19q13.13-q13.43 (69.53-101.1 cM; P = 0.00033), as well as LDL on 19p13.3-p12 (P = 0.00041). Suggestive evidence (i.e., P < 0.00860) for linkage was also observed for LDL on 19p12-q13.13, triglycerides on 7p11-q21.11 (63.72-93.29 cM), triglyceride/HDL on 7p11-q21.11 and 19p12-q13.13, and LDL/HDL on 16q11.2-q24.3 (65.2-130.4 cM) and 19p12-q13.13. Linkage for lipid traits has been previously observed on both chromosomes 7 and 19 in several unrelated studies and, together with the results of this meta-analysis, provide compelling evidence that these regions harbor important determinants of lipid levels in individuals with type 2 diabetes.

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Meta-analysis of genome-wide linkage studies of quantitative lipid traits in families ascertained for type 2 diabetes

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