Meta-Analysis of Genome-Wide Linkage Studies of Quantitative Lipid Traits in Families Ascertained for Type 2 Diabetes
- Alka Malhotra1,
- Steven C. Elbein2,
- Maggie C.Y. Ng3,
- Ravindranath Duggirala4,
- Rector Arya5,
- Giuseppina Imperatore6,
- Adebowale Adeyemo7,
- Toni I. Pollin8,
- Wen-Chi Hsueh9,
- Juliana C.N. Chan3,
- Charles Rotimi7,
- Robert L. Hanson10,
- Sandra J. Hasstedt11,
- Johanna K. Wolford1 and
- and the American Diabetes Association GENNID Study Group*
- 1Diabetes and Obesity Research Unit, Translational Genomics Research Institute, Phoenix, Arizona
- 2Endocrinology Section, University of Arkansas, Little Rock, Arkansas
- 3Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, Hong Kong
- 4Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas
- 5Division of Clinical Epidemiology, University of Texas Health Sciences Center, San Antonio, Texas
- 6Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, Georgia
- 7National Human Genome Center, Howard University, Washington, DC
- 8Division of Endocrinology, Diabetes, and Nutrition, University of Maryland, Baltimore, Maryland
- 9Department of Medicine, University of California San Francisco, San Francisco, California
- 10Diabetes and Arthritis Epidemiology Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona
- 11Human Genetics Department, University of Utah, Salt Lake City, Utah
- Address correspondence and reprint requests to Alka Malhotra, Diabetes and Obesity Research Unit, Genetic Basis of Human Disease, Translational Genomics Research Institute, 445 N. 5th St., Phoenix, AZ 85004. E-mail: amalhotra{at}tgen.org
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.
- AADM, Africa-America Diabetes Mellitus
- AFDS, Amish Family Diabetes Study
- CHD, coronary heart disease
- GENNID, Genetics of NIDDM
- GSMA, Genome Scan Meta-Analysis
- HKFDS, Hong Kong Family Diabetes Study
- LOD, logarithm of odds
- SAFADS, San Antonio Family Diabetes Study
Footnotes
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* A complete list of the American Diabetes Association GENNID Study Group members can be found in the acknowledgments.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted December 12, 2006.
- Received July 28, 2006.
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