Mf. Feitosa et al., Quantitative-trait loci influencing body-mass index reside on chromosomes 7 and 13: The National Heart, Lung, and Blood Institute Family Heart Study, AM J HU GEN, 70(1), 2002, pp. 72-82
Citations number
65
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Molecular Biology & Genetics
Obesity is a risk factor for many chronic diseases, including glucose intol
erance, lipid disorders, hypertension, and coronary heart disease. Even tho
ugh the body-mass index (BMI) is a heterogeneous phenotype reflecting the a
mount of fat, lean mass, and body build, several studies have provided evid
ence of one or two major loci contributing to the variation in this complex
trait. We sought to identify loci with potential influence on BMI in the d
ata obtained from National Heart, Lung, and Blood Institute Family Heart St
udy. Two complementary samples were studied: (a) 1, 184 subjects in 317 sib
ships, with 243 markers typed by the Utah Molecular Genetics Laboratory (UM
GL) and (b) 3,027 subjects distributed among 401 three-generation families,
with 404 markers typed by the Mammalian Genotyping Service (MGS). A genome
scan using a variance-components-based linkage approach was performed for
each sample, as well as for the combined sample, in which the markers from
each analysis were placed on a common genetic map. There was strong evidenc
e for linkage on chromosome 7q32.3 in each sample: the maximum multipoint L
OD scores were 4.7 (P<10(-3)) at marker GATA43C11 and 3.2 (P = .00007) at m
arker D7S1804, for the MGS and UMGL samples, respectively. The linkage resu
lt is replicated by the consistent evidence from these two complementary su
bsets. Furthermore, the evidence for linkage was maintained in the combined
sample, with a LOD score of 4.9 (P<10(-5)) for both markers, which map to
the same location. This signal is very near the published location for the
leptin gene, which is the most prominent candidate gene in this region. For
the combined-sample analysis, evidence of linkage was also found on chromo
some 13q14, with D13S257 (LOD score 3.2, P = .00006), and other, weaker sig
nals (LOD scores 1.5-1. 9) were found on chromosomes 1, 2, 3, 5, 6, 14, and
15.