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Association of Lead Exposure and Untargeted Metabolomics with BMI and Hormones in Adolescence
Author(s) -
Peterson Karen E.,
Dolinoy D,
Burant C,
Lee J.,
Sanchez B,
Zhang Z,
Yang T C.,
Goodrich J,
Ettinger A,
Meeker J,
Hu H,
Solano M,
Wang N,
TellezRojo MM
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1073.14
Subject(s) - metabolomics , endocrinology , body mass index , medicine , hormone , testosterone (patch) , metabolite , leptin , physiology , biology , chemistry , obesity , bioinformatics
Lead, an endocrine disrupting chemical (EDC), has been related to delays in weight and pubertal onset, but limited data account for metabolic mechanisms. We examined the additional variance in Body Mass Index (BMI), estradiol and testosterone among n=40 children aged 7–15 yr predicted by metabolomics, using a multi‐index model with variable selection to construct 2 indices for % methylation of CpG sites in utero and peripuberty of 4 candidate genes associated with physical growth and 2 indices each built from 317 metabolites with known functions and 440 so called “known‐unknown” compounds. After adjusting for child sex, age, leptin, blood lead at 4 yr and % methylation, the R 2 for BMI increased from 0.81 to 0.95, when metabolites were included in the model. For estradiol and total testosterone, the R 2 increased from 0.51 and 0.33, without metabolites, to 0.95 and 0.94 with metabolites, respectively. Using Metscape 2.0 to visualize the pathways associated with lead exposure, we found bile acid, amino acid and nucleotide metabolism were enriched. Results suggest our capacity to predict BMI, and hormonal markers of sexual maturation related to EDCs is markedly improved with inclusion of metabolites. Research support: NIEHS/EPA P20 ES01817101/RD834800; NIEHS R01 ES007821 ; P30 ES017885 ; P30 DK 089503.