Genome-wide scan for adiposity-related phenotypes in adults from American Samoa
Genome-wide scan for adiposity-related phenotypes in adults from American Samoa
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DOI：
10.1038/sj.ijo.0803675
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发表时间：
2007-12-01
影响因子：
4.9
通讯作者：
McGarvey, S. T.
中科院分区：
文献类型：
--
作者：
Dai, F.;Keighley, E. D.;McGarvey, S. T.
目的：检测影响肥胖相关表型的数量性状基因座，这些表型通过体重指数（BMI）、腹围（ABDCIR）、体脂百分比（% BFAT）和空腹血清瘦素和脂联素进行评估，使用来自美属萨摩亚的家族的全基因组连锁扫描。设计：基于家族的连锁分析，先证者和家族成员被诊断为肥胖。共有583个表型的美属萨摩亚成年人，其中578个基因分型在34 pediegrees.Measurements：共377个常染色体和18个X染色体微卫星标记进行了分型，跨越基因组的平均间距约为10厘米。使用方差分量法和SOLAR/LOKI软件计算多点LOD（比值对数）评分。同时评估的协变量为年龄、性别、教育、农场工作和吸烟，显著性水平为0.1。由于随机性质的LOKI，我们报告的平均值的最大LOD得分从10 runs.Results：显着的连锁瘦素被发现在6q32.2与LOD为3.83。与瘦素连锁的位点分别为16 q21：LOD = 2.98，1q42.2：LOD = 1.97，5q11.2：LOD = 2.08，12q24.23：LOD = 2.00，19p13.3：LOD = 2.05，脂联素与13q33.1-q22.1：LOD = 2.41，% BFAT与16q12.2-q21：LOD = 2.24，ABDCIR与16q23.1连锁：LOD = 1.95; %BFAT校正的leptin与14 q12连锁，LOD = 2.01; %BFAT校正的ABDCIR与1q31.1连锁，LOD = 2.36;与3q27.3-q28连锁，LOD = 2.10;与12p12.3连锁，LOD = 2.04。我们发现了强有力的证据，6q23.2上的一个主要位点影响血清瘦素水平在美属萨摩亚人。双变量连锁分析显示，16 q21区域似乎具有对表型BMI、% BFAT、瘦素和ABDCIR具有显著多效性效应的易感基因座。在整个基因组中检测到其他几个不同意义的基因座。
Objective: To detect quantitative trait loci influencing adiposity-related phenotypes assessed by body mass index (BMI), abdominal circumference (ABDCIR), percent body fat (% BFAT) and fasting serum leptin and adiponectin using a whole genome linkage scan of families from American Samoa.Design: Family-based linkage analysis, the probands and family members were unselected for obesity.Subjects: A total of 583 phenotyped American Samoan adults, of which 578 were genotyped in 34 pedigrees.Measurements: A total of 377 autosomal and 18 X chromosome microsatellite markers were typed at an approximate average spacing of 10 CM spanning the genome. Multipoint LOD ( logarithm of the odds) scores were calculated using variance-components approaches and SOLAR/LOKI software. The covariates simultaneously evaluated were age, sex, education, farm work and cigarette smoking, with a significance level of 0.1. Due to the stochastic nature of LOKI, we report the average of maximum LOD scores from 10 runs.Results: Significant linkage to leptin was found at 6q32.2 with LOD of 3.83. Suggestive linkage to leptin was found at 16q21:LOD = 2.98, 1q42.2: LOD = 1.97, 5q11.2: LOD = 2.08, 12q24.23: LOD = 2.00, 19p13.3: LOD = 2.05; adiponectin was linked to 13q33.1-q22.1: LOD = 2.41; % BFAT was linked to 16q12.2-q21, LOD = 2.24; ABDCIR was linked to 16q23.1: LOD = 1.95; % BFAT-adjusted leptin to 14q12, LOD = 2.01; % BFAT-adjusted ABDCIR to 1q31.1, LOD = 2.36, to 3q27.3-q28, LOD = 2.10 and to 12p12.3, LOD = 2.04.Conclusion: We found strong evidence for a major locus on 6q23.2 influencing serum leptin levels in American Samoans. The 16q21 region appears to harbor a susceptibility locus that has significant pleiotrophic effects on phenotypes BMI, % BFAT, leptin and ABDCIR as shown by bivariate linkage analyses. Several other loci of varying significance were detected across the genome.