| Quantitative trait loci on chromosome 8q24 for pancreatic beta-cell function and 7q11 for insulin sensitivity in obese nondiabetic white and black families: evidence from genome-wide linkage scans in the NHLBI Hypertension Genetic Epidemiology Network (HyperGEN) study. | |
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MedLine Citation:
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PMID: 16443794 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Genome-wide linkage scans were carried out using a multipoint variance components method in white and black families of the NHLBI Hypertension Genetic Epidemiology Network (HyperGEN) study to identify quantitative trait loci (QTLs) for pancreatic beta-cell function and insulin sensitivity estimated through the newly released nonlinear computer version of homeostasis model assessment 2. Participants fasting <8 h, with diagnosed type 2 diabetes, or taking blood glucose or blood lipid-lowering medications were excluded. Both phenotypes were adjusted separately by race and sex for the effects of age, BMI, and field center before linkage scans using 370 microsatellite markers were performed. A total of 685 white families (1,180 sibpairs) and 773 black families (775 sibpairs) were evaluated as well as subsets including 267 obese white families (757 sibpairs) and 427 obese black families (599 sibpairs) identified through tree-linkage analyses using interacting covariates of age, sex, and BMI. For beta-cell function in the obese white families, significant (logarithm of odds [LOD] score >3.6) evidence supporting linkages was detected on chromosome 8q24 at D8S1179 (135 cM, LOD score 4.2, empirical P = 0.002) and at D8S1128 (140 cM, LOD score 3.7, empirical P = 0.003). In addition, two regions supported linkage for insulin sensitivity index in the obese black families on chromosome 7q11 at D7S3046 (79 cM, LOD score 3.0, empirical P = 0.018) and on chromosome 6q26 at D6S1277 (173 cM, LOD score 3.0, empirical P = 0.018). Reducing clinical heterogeneity using obesity data and improved estimates of beta-cell function and insulin sensitivity may have permitted identification of a QTL on chromosome 8q24 for beta-cell function in the presence of estimated insulin resistance and a QTL on chromosome 7q11 for insulin sensitivity. These regions replicate previous reports for type 2 diabetes-associated traits. |
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Authors:
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Ping An; Barry I Freedman; Stephen S Rich; Stephen A Mandel; Donna K Arnett; Richard H Myers; Yii-Der I Chen; Steven C Hunt; D C Rao |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Diabetes Volume: 55 ISSN: 0012-1797 ISO Abbreviation: Diabetes Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-01-30 Completed Date: 2006-03-23 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: United States |
Other Details:
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Languages: eng Pagination: 551-8 Citation Subset: AIM; IM |
Affiliation:
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Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA. anping@wustl.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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African Continental Ancestry Group
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genetics* Chromosomes, Human, Pair 7 / genetics* Chromosomes, Human, Pair 8 / genetics* Diabetes Mellitus, Type 2 / genetics European Continental Ancestry Group / genetics* Genome, Human Humans Hypertension / genetics Insulin Resistance / genetics* Insulin-Secreting Cells / physiology* Linkage (Genetics) Obesity / genetics* Quantitative Trait Loci / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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U10 HL54471/HL/NHLBI NIH HHS; U10 HL54472/HL/NHLBI NIH HHS; U10 HL54473/HL/NHLBI NIH HHS; U10 HL54495/HL/NHLBI NIH HHS; U10 HL54496/HL/NHLBI NIH HHS; U10 HL54497/HL/NHLBI NIH HHS; U10 HL54509/HL/NHLBI NIH HHS; U10 HL54515/HL/NHLBI NIH HHS |
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