Saunders Catherine L, Chiodini Benedetta D, Sham Pak, Lewis Cathryn M, Abkevich Victor, Adeyemo Adebowale A, de Andrade Mariza, Arya Rector, Berenson Gerald S, Blangero John, Boehnke Michael, Borecki Ingrid B, Chagnon Yvon C, Chen Wei, Comuzzie Anthony G, Deng Hong-Wen, Duggirala Ravindranath, Feitosa Mary F, Froguel Philippe, Hanson Robert L, Hebebrand Johannes, Huezo-Dias Patricia, Kissebah Ahmed H, Li Weidong, Luke Amy, Martin Lisa J, Nash Matthew, Ohman Miina, Palmer Lyle J, Peltonen Leena, Perola Markus, Price R Arlen, Redline Susan, Srinivasan Sathanur R, Stern Michael P, Stone Steven, Stringham Heather, Turner Stephen, Wijmenga Cisca, Collier David A
King's College London, Guy's, King's & St. Thomas' School of Medicine, London, United Kingdom.
Obesity (Silver Spring). 2007 Sep;15(9):2263-75. doi: 10.1038/oby.2007.269.
The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis.
We identified 37 published studies containing data on over 31,000 individuals from more than >10,000 families and obtained genome-wide logarithm of the odds (LOD) scores, non-parametric linkage (NPL) scores, or maximum likelihood scores (MLS). BMI was analyzed in a pooled set of all studies, as a subgroup of 10 studies that used BMI-defined obesity, and for subgroups ascertained through type 2 diabetes, hypertension, or subjects of European ancestry.
Bins at chromosome 13q13.2- q33.1, 12q23-q24.3 achieved suggestive evidence of linkage to BMI in the pooled analysis and samples ascertained for hypertension. Nominal evidence of linkage to these regions and suggestive evidence for 11q13.3-22.3 were also observed for BMI-defined obesity. The FTO obesity gene locus at 16q12.2 also showed nominal evidence for linkage. However, overall distribution of summed rank p values <0.05 is not different from that expected by chance. The strongest evidence was obtained in the families ascertained for hypertension at 9q31.1-qter and 12p11.21-q23 (p < 0.01).
Despite having substantial statistical power, we did not unequivocally implicate specific loci for BMI or obesity. This may be because genes influencing adiposity are of very small effect, with substantial genetic heterogeneity and variable dependence on environmental factors. However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further.
本研究旨在通过非参数基因组扫描荟萃分析，对体重指数（BMI）及BMI定义的肥胖症的遗传连锁数据进行全面评估。
我们确定了37项已发表的研究，这些研究包含来自10000多个家庭的31000多名个体的数据，并获得了全基因组优势对数（LOD）分数、非参数连锁（NPL）分数或最大似然分数（MLS）。在所有研究的汇总集中分析BMI，作为使用BMI定义肥胖症的10项研究的亚组，并针对通过2型糖尿病、高血压或欧洲血统受试者确定的亚组进行分析。
在汇总分析以及为高血压确定的样本中，13号染色体q13.2 - q33.1、12号染色体q23 - q24.3区域的区间获得了与BMI连锁的提示性证据。对于BMI定义的肥胖症，也观察到了与这些区域连锁的名义证据以及11号染色体q13.3 - 22.3区域的提示性证据。位于16号染色体q12.2的FTO肥胖基因位点也显示出连锁的名义证据。然而，总和秩p值<0.05的总体分布与随机预期的分布没有差异。在为高血压确定的家庭中，9号染色体q31.1 - qter和12号染色体p11.21 - q23区域获得了最强的证据（p < 0.01）。
尽管具有强大的统计效力，但我们并未明确指出BMI或肥胖症的特定基因座。这可能是因为影响肥胖的基因效应非常小，存在大量的遗传异质性以及对环境因素的可变依赖性。然而，FTO基因定位于肥胖症排名最高的区间之一这一观察结果很有趣，虽然这并非对该方法的验证，但表明本研究中确定的其他潜在基因座应进一步研究。
