Genome-wide linkage scan to identify loci associated with type 2 diabetes and blood lipid phenotypes in the Sikh Diabetes Study
Autor: | Jai Singh, Narinder K. Mehra, Christopher E. Aston, Dharambir K. Sanghera, Sarju Ralhan, Gurpreet Singh Wander, Latonya F. Been, Kamboh Mi, Robert E. Ferrell |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Male
Very low-density lipoprotein Heredity Genetic Linkage Blood lipids lcsh:Medicine Genome-wide association study 030204 cardiovascular system & hematology Biochemistry Lipoprotein Metabolism Cohort Studies chemistry.chemical_compound 0302 clinical medicine lcsh:Science 2. Zero hunger Genetics 0303 health sciences education.field_of_study Multidisciplinary Linkage (Genetics) Genomics Lipids 3. Good health Sterols Phenotype Chromosomal region Blood Chemistry Female lipids (amino acids peptides and proteins) Research Article Lipoproteins Population Quantitative Trait Loci Quantitative trait locus Biology 03 medical and health sciences Genetic linkage Genome Analysis Tools Genome-Wide Association Studies Humans education Genetic Association Studies 030304 developmental biology Plasma Proteins Cholesterol lcsh:R Proteins Computational Biology Human Genetics Lipid Metabolism Metabolism chemistry Diabetes Mellitus Type 2 Genetics of Disease lcsh:Q Genome-Wide Association Study |
Zdroj: | PLoS ONE, Vol 6, Iss 6, p e21188 (2011) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | 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 S(all) 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. |
Databáze: | OpenAIRE |
Externí odkaz: |