TY - JOUR
T1 - Metabolic Signatures of Youth Exposure to Mixtures of Per-and Polyfluoroalkyl Substances
T2 - A Multi-Cohort Study
AU - Goodrich, Jesse A.
AU - Walker, Douglas I.
AU - He, Jingxuan
AU - Lin, Xiangping
AU - Baumert, Brittney O.
AU - Hu, Xin
AU - Alderete, Tanya L.
AU - Chen, Zhanghua
AU - Valvi, Damaskini
AU - Fuentes, Zoe C.
AU - Rock, Sarah
AU - Wang, Hongxu
AU - Berhane, Kiros
AU - Gilliland, Frank D.
AU - Goran, Michael I.
AU - Jones, Dean P.
AU - Conti, David V.
AU - Chatzi, Leda
N1 - Funding Information:
The results reported herein correspond to specific aims of grant R01ES029944 from the National Institutes of Health/ National Institute of Environmental Health Science (NIH/ NIEHS) (to L.C.). Funding for the Study of Latino Adolescents at Risk (SOLAR) came from the NIH grant R01DK59211 (to M.I.G.), and funding for the MetaAir study came from the Southern California Children’s Environmental Health Center grants funded by the NIEHS (5P01ES022845-03, 5P30ES007048, 5P01ES011627), the U.S. Environmental Protection Agency (RD83544101), and the Hastings Foundation. Additional funding from NIH supported L.C. (R01ES030691, R01ES030364, R21ES029681, R21ES028903, and P30ES007048), J.A.G. (T32ES013678, R25GM143298), Z.C. (R00ES027870), D.V. (R01ES033688, R21ES029328, K12ES033594, P30ES023515), D.I.W. (U2CES030859, R01ES032831), D.V.C. (P01CA196569, P30ES007048, R01ES030691, R01ES030364, R21ES029681, R21ES028903), T.L.A (R00ES027853, P50MD017344), and D.P.J. (U2CES030163, P30ES019776, R24ES029490, R01ES032189, R21ES031824).
Publisher Copyright:
© 2023, Public Health Services, US Dept of Health and Human Services. All rights reserved.
PY - 2023/2
Y1 - 2023/2
N2 - BACKGROUND: Exposure to per-and polyfluoroalkyl substances (PFAS) is ubiquitous and has been associated with an increased risk of several cardio-metabolic diseases. However, the metabolic pathways linking PFAS exposure and human disease are unclear. OBJECTIVE: We examined associations of PFAS mixtures with alterations in metabolic pathways in independent cohorts of adolescents and young adults. METHODS: Three hundred twelve overweight/obese adolescents from the Study of Latino Adolescents at Risk (SOLAR) and 137 young adults from the Southern California Children’s Health Study (CHS) were included in the analysis. Plasma PFAS and the metabolome were determined using liquid-chromatography/high-resolution mass spectrometry. A metabolome-wide association study was performed on log-transformed metabolites using Bayesian regression with a g-prior specification and g-computation for modeling exposure mixtures to estimate the impact of exposure to a mixture of six ubiquitous PFAS (PFOS, PFHxS, PFHpS, PFOA, PFNA, and PFDA). Pathway enrichment analysis was performed using Mummichog and Gene Set Enrichment Analysis. Significance across cohorts was determined using weighted Z-tests. RESULTS: In the SOLAR and CHS cohorts, PFAS exposure was associated with alterations in tyrosine metabolism (meta-analysis p = 0:00002) and de novo fatty acid biosynthesis (p = 0:03), among others. For example, when increasing all PFAS in the mixture from low (∼ 30th percentile) to high (∼ 70th percentile), thyroxine (T4), a thyroid hormone related to tyrosine metabolism, increased by 0.72 standard deviations (SDs; equivalent to a standardized mean difference) in the SOLAR cohort (95% Bayesian credible interval (BCI): 0.00, 1.20) and 1.60 SD in the CHS cohort (95% BCI: 0.39, 2.80). Similarly, when going from low to high PFAS exposure, arachidonic acid increased by 0.81 SD in the SOLAR cohort (95% BCI: 0.37, 1.30) and 0.67 SD in the CHS cohort (95% BCI: 0.00, 1.50). In general, no individual PFAS appeared to drive the observed associations. DISCUSSION: Exposure to PFAS is associated with alterations in amino acid metabolism and lipid metabolism in adolescents and young adults. https:// doi.org/10.1289/EHP11372.
AB - BACKGROUND: Exposure to per-and polyfluoroalkyl substances (PFAS) is ubiquitous and has been associated with an increased risk of several cardio-metabolic diseases. However, the metabolic pathways linking PFAS exposure and human disease are unclear. OBJECTIVE: We examined associations of PFAS mixtures with alterations in metabolic pathways in independent cohorts of adolescents and young adults. METHODS: Three hundred twelve overweight/obese adolescents from the Study of Latino Adolescents at Risk (SOLAR) and 137 young adults from the Southern California Children’s Health Study (CHS) were included in the analysis. Plasma PFAS and the metabolome were determined using liquid-chromatography/high-resolution mass spectrometry. A metabolome-wide association study was performed on log-transformed metabolites using Bayesian regression with a g-prior specification and g-computation for modeling exposure mixtures to estimate the impact of exposure to a mixture of six ubiquitous PFAS (PFOS, PFHxS, PFHpS, PFOA, PFNA, and PFDA). Pathway enrichment analysis was performed using Mummichog and Gene Set Enrichment Analysis. Significance across cohorts was determined using weighted Z-tests. RESULTS: In the SOLAR and CHS cohorts, PFAS exposure was associated with alterations in tyrosine metabolism (meta-analysis p = 0:00002) and de novo fatty acid biosynthesis (p = 0:03), among others. For example, when increasing all PFAS in the mixture from low (∼ 30th percentile) to high (∼ 70th percentile), thyroxine (T4), a thyroid hormone related to tyrosine metabolism, increased by 0.72 standard deviations (SDs; equivalent to a standardized mean difference) in the SOLAR cohort (95% Bayesian credible interval (BCI): 0.00, 1.20) and 1.60 SD in the CHS cohort (95% BCI: 0.39, 2.80). Similarly, when going from low to high PFAS exposure, arachidonic acid increased by 0.81 SD in the SOLAR cohort (95% BCI: 0.37, 1.30) and 0.67 SD in the CHS cohort (95% BCI: 0.00, 1.50). In general, no individual PFAS appeared to drive the observed associations. DISCUSSION: Exposure to PFAS is associated with alterations in amino acid metabolism and lipid metabolism in adolescents and young adults. https:// doi.org/10.1289/EHP11372.
UR - http://www.scopus.com/inward/record.url?scp=85148772631&partnerID=8YFLogxK
U2 - 10.1289/EHP11372
DO - 10.1289/EHP11372
M3 - Article
C2 - 36821578
AN - SCOPUS:85148772631
SN - 0091-6765
VL - 131
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
IS - 2
M1 - 027005
ER -