Zhang W, Maniatis N, Rodriguez S, Miller G J, Day I N M, Gaunt T R, Collins A, Morton N E
Human Genetics Division, University of Southampton, School of Medicine, Duthie Building (MP 808), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
Ann Hum Genet. 2006 Nov;70(Pt 6):848-56. doi: 10.1111/j.1469-1809.2006.00290.x.
Previous analyses have provided evidence for one or more loci affecting body weight in the H19-IGF2-INS-TH region on chromosome 11p15. To identify the location of a possible causal locus or loci we applied association analysis by composite likelihood to a large cohort under the Malecot model for body weight. A random sample of 2731 men in the UK were typed for eleven single nucleotide polymorphisms (SNPs) in IGF2, two SNPs in H19, one SNP in INS and one microsatellite marker in the TH genes. Using F tests appropriate to small marker sets, the superiority of regression over correlation was confirmed. All the evidence for association came from IGF2, with P= 0.007 for height-adjusted weight and P= 0.019 for weight additionally adjusted for smoking and alcohol drinking. Although the estimated point location for the suspected causal variant was close to IGF2 ApaI, the 95% confidence and support intervals covered most of IGF2 but none of the other loci. Identification of the causal SNP or SNPs within IGF2 will require typing of more variants in this region.
以往的分析已为11号染色体p15区域中H19 - IGF2 - INS - TH区域内一个或多个影响体重的基因座提供了证据。为了确定可能的因果基因座的位置，我们在Malecot体重模型下，对一个大型队列应用复合似然关联分析。对英国的2731名男性随机样本进行了IGF2基因中11个单核苷酸多态性（SNP）、H19基因中2个SNP、INS基因中1个SNP以及TH基因中1个微卫星标记的分型。使用适用于小标记集的F检验，证实了回归优于相关性。所有关联证据均来自IGF2，身高调整体重的P值为0.007，吸烟和饮酒因素调整后的体重P值为0.019。尽管疑似因果变异的估计点位置接近IGF2 ApaI，但95%置信区间和支持区间覆盖了大部分IGF2区域，而未覆盖其他任何基因座。要确定IGF2基因内的因果SNP，需要对该区域更多的变异进行分型。
