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

Research output: Contribution to journalArticle

30 Scopus citations

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 languageEnglish (US)
Pages (from-to)890-896
Number of pages7
JournalDiabetes
Volume56
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

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