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Genome-wide linkage scan to identify loci associated with type 2 diabetes and blood lipid phenotypes in the sikh diabetes study

Sanghera, DK and Been, LF and Ralhan, S and Wander, GS and Mehra, NK and Singh, JR and Ferrell, RE and Kamboh, MI and Aston, CE (2011) Genome-wide linkage scan to identify loci associated with type 2 diabetes and blood lipid phenotypes in the sikh diabetes study. PLoS ONE, 6 (6).

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In this investigation, we have carried out an autosomal genome-wide linkage analysis to map genes associated with type 2 diabetes (T2D) and five quantitative traits of blood lipids including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, and triglycerides in a unique family-based cohort from the Sikh Diabetes Study (SDS). A total of 870 individuals (526 male/344 female) from 321 families were successfully genotyped using 398 polymorphic microsatellite markers with an average spacing of 9.26 cM on the autosomes. Results of non-parametric multipoint linkage analysis using Sall statistics (implemented in Merlin) did not reveal any chromosomal region to be significantly associated with T2D in this Sikh cohort. However, linkage analysis for lipid traits using QTL-ALL analysis revealed promising linkage signals with p≤0.005 for total cholesterol, LDL cholesterol, and HDL cholesterol at chromosomes 5p15, 9q21, 10p11, 10q21, and 22q13. The most significant signal (p = 0.0011) occurred at 10q21.2 for HDL cholesterol. We also observed linkage signals for total cholesterol at 22q13.32 (p = 0.0016) and 5p15.33 (p = 0.0031) and for LDL cholesterol at 10p11.23 (p = 0.0045). Interestingly, some of linkage regions identified in this Sikh population coincide with plausible candidate genes reported in recent genome-wide association and meta-analysis studies for lipid traits. Our study provides the first evidence of linkage for loci associated with quantitative lipid traits at four chromosomal regions in this Asian Indian population from Punjab. More detailed examination of these regions with more informative genotyping, sequencing, and functional studies should lead to rapid detection of novel targets of therapeutic importance. © 2011 Sanghera et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Sanghera, DK
Been, LF
Ralhan, S
Wander, GS
Mehra, NK
Singh, JR
Ferrell, RErferrell@pitt.eduRFERRELL
Kamboh, MIkamboh@pitt.eduKAMBOH
Aston, CE
ContributionContributors NameEmailPitt UsernameORCID
Date: 22 June 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 6
DOI or Unique Handle: 10.1371/journal.pone.0021188
Schools and Programs: School of Public Health > Human Genetics
Refereed: Yes
MeSH Headings: Cohort Studies; Diabetes Mellitus, Type 2--genetics; Female; Genetic Linkage; Genome-Wide Association Study; Humans; Lipids--blood; Male; Phenotype; Quantitative Trait Loci
Other ID: NLM PMC3116872
PubMed Central ID: PMC3116872
PubMed ID: 21698157
Date Deposited: 05 Sep 2012 17:33
Last Modified: 22 Jun 2021 15:55


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