Genome-wide scan of obesity in the old order Amish

被引:71
作者
Hsueh, WC
Mitchell, BD
Schneider, JL
St Jean, PL
Pollin, TI
Ehm, MG
Wagner, MJ
Burns, DK
Sakul, H
Bell, CJ
Shuldiner, AR
机构
[1] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA
[2] SW Fdn Biomed Res, San Antonio, TX 78245 USA
[3] Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA
[4] Axys Pharmaceut, La Jolla, CA 92037 USA
关键词
D O I
10.1210/jc.86.3.1199
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 fi om obesity loci previously reported in French and German Caucasians. Two additional linkage signals for this trait were observed on chromosomes 7q (lod = 1.77, similar to 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.
引用
收藏
页码:1199 / 1205
页数:7
相关论文
共 49 条
[41]   Replication of linkage studies of complex traits: An examination of variation in location estimates [J].
Roberts, SB ;
MacLean, CJ ;
Neale, MC ;
Eaves, LJ ;
Kendler, KS .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 65 (03) :876-884
[42]  
Spiegelman B M, 1997, Eur J Med Res, V2, P457
[43]   A leptin missense mutation associated with hypogonadism and morbid obesity [J].
Strobel, A ;
Issad, T ;
Camoin, L ;
Ozata, M ;
Strosberg, AD .
NATURE GENETICS, 1998, 18 (03) :213-215
[44]   STIMULATION OF ADIPOGENESIS IN FIBROBLASTS BY PPAR-GAMMA-2, A LIPID-ACTIVATED TRANSCRIPTION FACTOR [J].
TONTONOZ, P ;
HU, ED ;
SPIEGELMAN, BM .
CELL, 1994, 79 (07) :1147-1156
[45]   An autosomal genomic scan for loci linked to plasma leptin concentration in Pima Indians [J].
Walder, K ;
Hanson, RL ;
Kobes, S ;
Knowler, WC ;
Ravussin, E .
INTERNATIONAL JOURNAL OF OBESITY, 2000, 24 (05) :559-565
[46]   Agreement of skinfold measurement and bioelectrical impedance analysis (BIA) methods with dual energy X-ray absorptiometry (DEXA) in estimating total body fat in Anglo-Celtic Australians [J].
Wattanapenpaiboon, N ;
Lukito, W ;
Strauss, BJG ;
Hsu-Hage, BH ;
Wahlqvist, ML ;
Stroud, DB .
INTERNATIONAL JOURNAL OF OBESITY, 1998, 22 (09) :854-860
[47]   Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. I. Likelihood formulation and simulation results [J].
Williams, JT ;
Van Eerdewegh, P ;
Almasy, L ;
Blangero, J .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 65 (04) :1134-1147
[48]   Current estimates of the economic cost of obesity in the United States [J].
Wolf, AM ;
Colditz, GA .
OBESITY RESEARCH, 1998, 6 (02) :97-106
[49]   POSITIONAL CLONING OF THE MOUSE OBESE GENE AND ITS HUMAN HOMOLOG [J].
ZHANG, YY ;
PROENCA, R ;
MAFFEI, M ;
BARONE, M ;
LEOPOLD, L ;
FRIEDMAN, JM .
NATURE, 1994, 372 (6505) :425-432