American Association for Cancer Research
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Supplementary Figure 2 from Metabolomics in Epidemiology: Sources of Variability in Metabolite Measurements and Implications

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journal contribution
posted on 2023-03-31, 13:45 authored by Joshua N. Sampson, Simina M. Boca, Xiao Ou Shu, Rachael Z. Stolzenberg-Solomon, Charles E. Matthews, Ann W. Hsing, Yu Ting Tan, Bu-Tian Ji, Wong-Ho Chow, Qiuyin Cai, Da Ke Liu, Gong Yang, Yong Bing Xiang, Wei Zheng, Rashmi Sinha, Amanda J. Cross, Steven C. Moore

PDF file - 16K, The correlation of the (BIV) measured from PLCO and SPA.



Background: 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.Methods: 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.Results: 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.Conclusion: Metabolomics will require large, but feasible, sample sizes to detect the moderate effect sizes typical for epidemiologic studies.Impact: We offer guidelines for determining the sample sizes needed to conduct metabolomic studies in epidemiology. Cancer Epidemiol Biomarkers Prev; 22(4); 631–40. ©2013 AACR.