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.
authors.affiliation: Diabetes and Obesity Research Unit, Genetic Basis of Human Disease, Translational Genomics Research Institute, 445 N. 5th Street, Phoenix, AZ 85004, USA. amalhotra@tgen.org
authors.forename: Alka
authors.initials: A
authors.lastname: Malhotra
authors.forename: Steven C
authors.initials: SC
authors.lastname: Elbein
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.forename: Ravindranath
authors.initials: R
authors.lastname: Duggirala
authors.forename: Rector
authors.initials: R
authors.lastname: Arya
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Imperatore
authors.forename: Adebowale
authors.initials: A
authors.lastname: Adeyemo
authors.forename: Toni I
authors.initials: TI
authors.lastname: Pollin
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Hsueh
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
authors.forename: Charles
authors.initials: C
authors.lastname: Rotimi
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hanson
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Hasstedt
authors.forename: Johanna K
authors.initials: JK
authors.lastname: Wolford
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D050171:Dyslipidemias / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008297:Male; D010375:Pedigree; D040641:Quantitative Trait Loci / Q000235:genetics*; D044469:Racial Groups