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
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