Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of endurance exercise training in non-diabetic whites and blacks: the HERITAGE Family Study.
OBJECTIVE
Impaired insulin secretion, insulin action, insulin-independent glucose effectiveness, glucose tolerance and the associated abnormalities in insulin and glucose metabolism phenotypes are precursors of type 2 diabetes. Genome-wide multipoint variance component linkage scans were carried out using 654 markers to identify quantitative trait loci for insulin sensitivity, acute insulin response to glucose, disposition index and glucose effectiveness training responses in whites and blacks in the HERITAGE Family Study.


METHODS
These phenotypes were obtained from an IVGTT with the minimal model. The distributions of insulin sensitivity, acute insulin response to glucose and disposition index training responses (post-training minus baseline) were approximately normalised using a square-root transformation. All phenotypes were adjusted for the effects of age, BMI and their respective baseline values within sex and generation by race prior to linkage scans.


RESULTS
In blacks, a promising linkage with a maximum lod score of 3.1 on 19q (54-62 Mb) for glucose effectiveness training response was found. Six interesting linkages with lod scores of at least 1.0 were found for disposition index training response in whites. They included 1p (30 Mb), 3q (152 Mb), 6p (23-42 Mb), 7q (95-96 Mb), 10p (15 Mb) and 12q (119-126 Mb).


CONCLUSIONS
Quantitative trait loci for 20 weeks of endurance exercise training responses in insulin action and glucose metabolism phenotypes were found on chromosome 19q as well as 6p and 7q, with nominal (6p, 7q) but consistent (6p) linkages across the races.
An
P
P
Division of Biostatistics, Washington University School of Medicine, Campus Box 8067, 660 South Euclid Avenue, St Louis, MO, 63110, USA. anping@wustl.edu
Teran-Garcia
M
M
Rice
T
T
Rankinen
T
T
Weisnagel
S J
SJ
Bergman
R N
RN
Boston
R C
RC
Mandel
S
S
Stefanovski
D
D
Leon
A S
AS
Skinner
J S
JS
Rao
D C
DC
Bouchard
C
C
D000293:Adolescent; D000328:Adult; D044383:Black People; D015992:Body Mass Index; D002874:Chromosome Mapping; D005190:Family; D005260:Female; D005819:Genetic Markers; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009656:North America; D010641:Phenotype; D010807:Physical Endurance / Q000502:physiology*; D010809:Physical Fitness; D011236:Prediabetic State / Q000235:genetics*; D040641:Quantitative Trait Loci; D012016:Reference Values; D044465:White People
D005819:Genetic Markers