Engelman Corinne D, Brady Heather L, Baron Anna E, Norris Jill M
Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado, USA.
BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S90. doi: 10.1186/1471-2156-4-S1-S90.
Genes have been found to influence the age of onset of several diseases and traits. The occurrence of many chronic diseases, obesity included, appears to be strongly age-dependent. However, an analysis of potential age of onset genes for obesity has yet to be reported. There are at least two analytic methods for determining an age of onset gene. The first is to consider a person affected if they possess the trait before a certain age (an early age of onset phenotype). The second is to define the phenotype based on the residual from a survival analysis.
No regions provided evidence for linkage at the more stringent level of p < 0.001. However, five regions showed consistent suggestive evidence for linkage (one marker with p < 0.01 and a second contiguous marker at p < 0.05). These regions were chromosome 1 (280-294 cM) and chromosome 16 (56-64 cM) for overweight using the survival analysis residual method and chromosome 13 (102-122 cM), chromosome 17 (127-138 cM), and chromosome 19 (23-47 cM) for obese before age 35.
Only one region (chromosome 19 at 23-47 cM) showed somewhat consistent results between the two analytic methods. Potential reasons for inconsistent results between the two methods, as well as their strengths and weaknesses, are discussed. The use of both methods together to explore the genetics of the age of onset of a trait may prove to be beneficial in determining a gene that is linked only to an early age of onset phenotype versus one that determines age of onset through all age groups.
已发现基因会影响多种疾病和性状的发病年龄。包括肥胖症在内的许多慢性疾病的发生似乎都强烈依赖于年龄。然而，尚未有关于肥胖症潜在发病年龄基因的分析报告。确定发病年龄基因至少有两种分析方法。第一种是如果一个人在特定年龄之前具有该性状（早发性表型），则认为其受到影响。第二种是基于生存分析的残差来定义表型。
在更为严格的p < 0.001水平上，没有区域提供连锁证据。然而，有五个区域显示出一致的连锁暗示性证据（一个标记的p < 0.01，相邻的第二个标记的p < 0.05）。使用生存分析残差法，超重相关的这些区域为1号染色体（280 - 294 cM）和16号染色体（56 - 64 cM）；35岁前肥胖相关的区域为13号染色体（102 - 122 cM）、17号染色体（127 - 138 cM）和19号染色体（23 - 47 cM）。
只有一个区域（19号染色体的23 - 47 cM）在两种分析方法之间显示出 somewhat 一致的结果。讨论了两种方法结果不一致的潜在原因及其优缺点。将两种方法结合起来探索性状发病年龄的遗传学，可能有助于确定仅与早发性表型相关的基因，还是通过所有年龄组来确定发病年龄的基因。 （注：“somewhat”直译为“有点”，在这里结合语境可理解为“某种程度上”，但题目要求不添加解释，所以保留原文）
