Genome scan for childhood and adolescent obesity in German families

被引:56
作者
Saar, K
Geller, F
Rüschendorf, F
Reis, A
Friedel, S
Schäuble, N
Nürnberg, P
Siegfried, W
Goldschmidt, HP
Schäfer, H
Ziegler, A
Remschmidt, H
Hinney, A
Hebebrand, J
机构
[1] Univ Marburg, Dept Child & Adolescent Psychiat, Clin Res Grp, D-35033 Marburg, Germany
[2] Max Delbruck Ctr, Mol Genet & Gene Mapping Ctr, Berlin, Germany
[3] Max Planck Inst Mol Genet, Berlin, Germany
[4] Univ Marburg, Inst Med Biometry & Epidemiol, Marburg, Germany
[5] Univ Erlangen Nurnberg, Inst Human Genet, D-8520 Erlangen, Germany
[6] Obes Treatment Ctr Insula, Berchtesgaden, Germany
[7] Spessartklin, Bad Orb, Germany
[8] Univ Lubeck, Inst Med Biometry & Stat, Lubeck, Germany
关键词
linkage analysis; BMI; body weight;
D O I
10.1542/peds.111.2.321
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Objective. Several genome scans have been performed for adult obesity. Because single formal genetic studies suggest a higher heritability of body weight in adolescence and because genes that influence body weight in adulthood might not be the same as those that are relevant in childhood and adolescence, we performed a whole genome scan. Methods. The genome scan was based on 89 families with 2 or more obese children (sample 1). The mean age of the index patients was 13.63+/-2.75 years. A total of 369 individuals were initially genotyped for 437 microsatellite markers. A second sample of 76 families was genotyped using microsatellite markers that localize to regions for which maximum likelihood binomial logarithm of the odd (MLB LOD) scores on use of the concordant sibling pair approach exceeded 0.7 in sample 1. Results. The regions with MLB LOD scores >0.7 were on chromosomes 1p32.3-p33, 2q37.1-q37.3, 4q21, 8p22, 9p21.3, 10p11.23, 11q11-q13.1, 14q24-ter, and 19p13q12 in sample 1; MLB LOD scores on chromosomes 8p and 19q exceeded 1.5. In sample 2, MLB LOD scores of 0.68 and 0.71 were observed for chromosomes 10p11.23 and 11q13, respectively. Conclusion. We consider that several of the peaks identified in other scans also gave a signal in this scan as promising for ongoing pursuits to identify relevant genes. The genetic basis of childhood and adolescent obesity might not differ that much from adult obesity.
引用
收藏
页码:321 / 327
页数:7
相关论文
共 67 条
[1]   Robustness and power of the maximum-likelihood-binomial and maximum-likelihood-scope methods, in multipoint linkage analysis of affected-sibship data [J].
Abel, L ;
Müller-Myhsok, B .
AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 63 (02) :638-647
[2]   Genomewide scans of complex human diseases:: True linkage is hard to find [J].
Altmüller, J ;
Palmer, LJ ;
Fischer, G ;
Scherb, H ;
Wjst, M .
AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 69 (05) :936-950
[3]  
Blum WF, 1997, J CLIN ENDOCR METAB, V82, P2904, DOI 10.1210/jc.82.9.2904
[4]   GENETIC-ASPECTS OF OBESITY [J].
BOUCHARD, C ;
PERUSSE, L .
PREVENTION AND TREATMENT OF CHILDHOOD OBESITY, 1993, 699 :26-35
[5]   Genome-wide search for genes related to the fat-free body mass in the Quebec family study [J].
Chagnon, YC ;
Borecki, IB ;
Pérusse, L ;
Roy, S ;
Lacaille, M ;
Chagnon, M ;
Ho-Kim, MA ;
Rice, T ;
Province, MA ;
Rao, DC ;
Bouchard, C .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2000, 49 (02) :203-207
[6]   Indication for linkage of the human OB gene region with extreme obesity [J].
Clement, K ;
Garner, C ;
Hager, J ;
Philippi, A ;
LeDuc, C ;
Carey, A ;
Harris, TJR ;
Jury, C ;
Cardon, LR ;
Basdevant, A ;
Demenais, F ;
GuyGrand, B ;
North, M ;
Froguel, P .
DIABETES, 1996, 45 (05) :687-690
[7]   A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction [J].
Clément, K ;
Vaisse, C ;
Lahlou, N ;
Cabrol, S ;
Pelloux, V ;
Cassuto, D ;
Gourmelen, M ;
Dina, C ;
Chambaz, J ;
Lacorte, JM ;
Basdevant, A ;
Bougneres, P ;
Lebouc, Y ;
Froguel, P ;
Guy-Grand, B .
NATURE, 1998, 392 (6674) :398-401
[8]   Establishing a standard definition for child overweight and obesity worldwide: international survey [J].
Cole, TJ ;
Bellizzi, MC ;
Flegal, KM ;
Dietz, WH .
BMJ-BRITISH MEDICAL JOURNAL, 2000, 320 (7244) :1240-1243
[9]   A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2 [J].
Comuzzie, AG ;
Hixson, JE ;
Almasy, L ;
Mitchell, BD ;
Mahaney, MC ;
Dyer, TD ;
Stern, MP ;
MacCluer, JW ;
Blangero, J .
NATURE GENETICS, 1997, 15 (03) :273-276
[10]   A major susceptibility locus influencing plasma triglyceride concentrations is located on chromosome 15q in Mexican Americans [J].
Duggirala, R ;
Blangero, D ;
Almasy, L ;
Dyer, TD ;
Williams, KL ;
Leach, RJ ;
O'Connell, P ;
Stern, MP .
AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 66 (04) :1237-1245