Independent confirmation of a major locus for obesity on chromosome 10.
Linkage results obtained in genome-wide scans for complex phenotypes require confirmation in independent samples. Recently, linkage of obesity to chromosome 10p12 with a maximal multipoint LOD score of 4.85 was reported upon use of an affected sib-pair approach including nuclear families in which the adult index case had a BMI > or = 40 kg/m2 and at least one further sibling had a BMI > or = 27 kg/m2 (Hager et al., 1998, Nat Genet 20:304-8). To attempt to replicate this linkage finding we genotyped 11 markers spanning approximately 23 cM from 10p13 to 10ql1 in a total of 386 individuals stemming from 93 nuclear families with two or more young obese offspring with a BMI > or = 90th age percentile. The highest multipoint maximum likelihood binomial (MLB) LOD score using the extreme concordant sib-pair approach in which one sib had a BMI > or = 95th percentile, and other sibs a BMI > or = 90th percentile was 2.32. Six markers yielded nominal p-values < 0.05, the highest two point MLB-LOD score of 2.45 (nominal p = 0.0004) was obtained for the marker TCF8. Transmission disequilibrium tests for the most frequent parental allele yielded no nominal p-value < 0.05. The linkage results confirm the presence of a major susceptibility locus for obesity in a region near the centromere on chromosome 10.
Hinney
A
A
Department of Child and Adolescent Psychiatry, University of Marburg, FRG.
Ziegler
A
A
Oeffner
F
F
Wedewardt
C
C
Vogel
M
M
Wulftange
H
H
Geller
F
F
Stübing
K
K
Siegfried
W
W
Goldschmidt
H P
HP
Remschmidt
H
H
Hebebrand
J
J
D000328:Adult; D015992:Body Mass Index; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009679:Nuclear Family; D009765:Obesity / Q000235:genetics*
D005819:Genetic Markers