Genome-wide scan of obesity in the Old Order Amish.
To identify the genetic determinants of typical obesity, we performed a genome-wide scan of obesity-related traits using data from the Amish. Multipoint linkage analysis was performed using a variance components procedure on body mass index (BMI), waist circumference, percentage of body fat, and serum leptin concentrations. All 672 individuals were genotyped for 357 markers in 22 autosomes. We observed modest evidence for linkage, with the maximum log odds (lod) scores for linkage for these traits occurring on chromosomes 3p (percentage of body fat: lod = 1.61, near the peroxisome proliferator-activated receptor-alpha gene), 14q (waist: lod = 1.80), and 16p (leptin: lod = 1.72; BMI: lod = 1.68). We also tested for linkage to BMI-adjusted leptin concentrations and observed suggestive evidence for linkage on chromosome 10p (lod = 2.73), approximately 10-20 cM telomeric from obesity loci previously reported in French and German Caucasians. Two additional linkage signals for this trait were observed on chromosomes 7q (lod = 1.77, approximately 20 cM from the leptin gene) and 14q (lod = 2.47). Follow-up studies may be warranted to pursue some of these linkage signals, especially those detected near known obesity candidate genes, and those in regions coinciding with linkage signals reported previously.
Hsueh
W C
WC
Southwest Foundation for Biomedical Research, San Antonio, Texas 78245, USA.
Mitchell
B D
BD
Schneider
J L
JL
St  Jean
P L
PL
Pollin
T I
TI
Ehm
M G
MG
Wagner
M J
MJ
Burns
D K
DK
Sakul
H
H
Bell
C J
CJ
Shuldiner
A R
AR
D000273:Adipose Tissue; D000328:Adult; D001823:Body Composition; D001824:Body Constitution; D015992:Body Mass Index; D002879:Chromosomes, Human, Pair 10; D002883:Chromosomes, Human, Pair 14; D002885:Chromosomes, Human, Pair 16; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000032:analysis / Q000235:genetics; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D010414:Pennsylvania; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012067:Religion; D014157:Transcription Factors / Q000235:genetics
D005819:Genetic Markers; D020738:Leptin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors