Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Rockville, MD 20852, USA.
Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):631-40. doi: 10.1158/1055-9965.EPI-12-1109. Epub 2013 Feb 8.
Metabolite levels within an individual vary over time. This within-individual variability, coupled with technical variability, reduces the power for epidemiologic studies to detect associations with disease. Here, the authors assess the variability of a large subset of metabolites and evaluate the implications for epidemiologic studies.
Using liquid chromatography/mass spectrometry (LC/MS) and gas chromatography-mass spectroscopy (GC/MS) platforms, 385 metabolites were measured in 60 women at baseline and year-one of the Shanghai Physical Activity Study, and observed patterns were confirmed in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening study.
Although the authors found high technical reliability (median intraclass correlation = 0.8), reliability over time within an individual was low. Taken together, variability in the assay and variability within the individual accounted for the majority of variability for 64% of metabolites. Given this, a metabolite would need, on average, a relative risk of 3 (comparing upper and lower quartiles of "usual" levels) or 2 (comparing quartiles of observed levels) to be detected in 38%, 74%, and 97% of studies including 500, 1,000, and 5,000 individuals. Age, gender, and fasting status factors, which are often of less interest in epidemiologic studies, were associated with 30%, 67%, and 34% of metabolites, respectively, but the associations were weak and explained only a small proportion of the total metabolite variability.
Metabolomics will require large, but feasible, sample sizes to detect the moderate effect sizes typical for epidemiologic studies.
We offer guidelines for determining the sample sizes needed to conduct metabolomic studies in epidemiology.
个体内部的代谢物水平随时间变化。这种个体内的变异性，加上技术变异性，降低了流行病学研究检测与疾病关联的能力。在这里，作者评估了大量代谢物的变异性，并评估了其对流行病学研究的影响。
使用液相色谱/质谱（LC/MS）和气相色谱-质谱（GC/MS）平台，在上海体力活动研究的基线和第 1 年对 60 名女性测量了 385 种代谢物，并在前列腺癌、肺癌、结直肠癌和卵巢癌筛查研究中证实了观察到的模式。
尽管作者发现了很高的技术可靠性（中位数组内相关系数=0.8），但个体内部的时间可靠性却很低。总的来说，测定的变异性和个体内部的变异性占大多数代谢物变异性的 64%。鉴于此，一种代谢物需要平均 3 倍的相对风险（比较“通常”水平上下四分位数）或 2 倍的相对风险（比较观察到的水平四分位数），才能在包括 500、1000 和 5000 名个体的 38%、74%和 97%的研究中检测到。年龄、性别和禁食状态等因素在流行病学研究中通常不太感兴趣，分别与 30%、67%和 34%的代谢物相关，但这些关联较弱，仅解释了代谢物总变异性的一小部分。
代谢组学将需要大但可行的样本量来检测流行病学研究中典型的中等效应大小。
我们为在流行病学中进行代谢组学研究确定所需样本量提供了指导方针。
