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Meta-Analysis of Genome-Wide Linkage Studies of Quantitative Lipid Traits in Families Ascertained for Type 2 Diabetes

Year: 2007
Type: review
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.
Source: Diabetes
DOI: 10.2337/db06-1057
Authors: 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
Institutions: Translational Genomics Research Institute, University of Utah, University of Arkansas Medical Center, Chinese University of Hong Kong, Texas Biomedical Research Institute, The University of Texas at San Antonio Health Science Center, Centers for Disease Control and Prevention, Howard University, University of Maryland, Baltimore, University of California, San Francisco, National Institute of Diabetes and Digestive and Kidney Diseases
Language: English
Subfield: Genetics
Open Access status: bronze
Funders: University of Hong Kong, Chinese University of Hong Kong, National Institutes of Health, National Human Genome Research Institute, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G2538070308, G3324463029, G474297630, G5413809117, G5540814443, G853394594, G895200619
OpenAlex ID: W1992286600
FWCI: 0.337
Cites: 23
Cited by: 37
Related to: 10