Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood

EpiGen Consortium

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: The early life environment may influence susceptibility to obesity and metabolic disease in later life through epigenetic processes. SLC6A4 is an important mediator of serotonin bioavailability, and has a key role in energy balance. We tested the hypothesis that methylation of the SLC6A4 gene predicts adiposity across the life course. Methods: DNA methylation at 5 CpGs within the SLC6A4 gene identified from a previous methyl binding domain array was measured by pyrosequencing. We measured DNA methylation in umbilical cord (UC) from children in the Southampton Women’s Survey cohort (n = 680), in peripheral blood from adolescents in the Western Australian Pregnancy Cohort Study (n = 812), and in adipose tissue from lean and obese adults from the UK BIOCLAIMS cohort (n = 81). Real-time PCR was performed to assess whether there were corresponding alterations in gene expression in the adipose tissue. Results: Lower UC methylation of CpG5 was associated with higher total fat mass at 4 years (p = 0.031), total fat mass at 6–7 years (p = 0.0001) and % fat mass at 6–7 years (p = 0.004). Lower UC methylation of CpG5 was also associated with higher triceps skinfold thickness at birth (p = 0.013), 6 months (p = 0.038), 12 months (p = 0.062), 2 years (p = 0.0003), 3 years (p = 0.00004) and 6–7 years (p = 0.013). Higher maternal pregnancy weight gain (p = 0.046) and lower parity (p = 0.029) were both associated with lower SLC6A4 CpG5 methylation. In adolescents, lower methylation of CpG5 in peripheral blood was associated with greater concurrent measures of adiposity including BMI (p ≤ 0.001), waist circumference (p = 0.011), subcutaneous fat (p ≤ 0.001) and subscapular, abdominal and suprailiac skinfold thicknesses (p = 0.002, p = 0.008, p = 0.004, respectively). In adipose tissue, methylation of both SLC6A4 CpG5 (p = 0.019) and expression of SLC6A4 (p = 0.008) was lower in obese compared with lean adults. Conclusions: These data suggest that altered methylation of CpG loci within SLC6A4 may provide a robust marker of adiposity across the life course.

Original languageEnglish
Pages (from-to)974-988
Number of pages15
JournalInternational Journal of Obesity
Volume43
Issue number5
Early online date8 Jan 2019
DOIs
Publication statusPublished - May 2019

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Adiposity
Epigenomics
Methylation
Parturition
Umbilical Cord
Adipose Tissue
Skinfold Thickness
Fats
DNA Methylation
Genetic Epigenesis
Pregnancy
Subcutaneous Fat
Metabolic Diseases
Waist Circumference
Parity
Biological Availability
Genes
Weight Gain
Real-Time Polymerase Chain Reaction
Serotonin

Cite this

@article{828c0c5172b242d0b94e50528ab8b09f,
title = "Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood",
abstract = "Background: The early life environment may influence susceptibility to obesity and metabolic disease in later life through epigenetic processes. SLC6A4 is an important mediator of serotonin bioavailability, and has a key role in energy balance. We tested the hypothesis that methylation of the SLC6A4 gene predicts adiposity across the life course. Methods: DNA methylation at 5 CpGs within the SLC6A4 gene identified from a previous methyl binding domain array was measured by pyrosequencing. We measured DNA methylation in umbilical cord (UC) from children in the Southampton Women’s Survey cohort (n = 680), in peripheral blood from adolescents in the Western Australian Pregnancy Cohort Study (n = 812), and in adipose tissue from lean and obese adults from the UK BIOCLAIMS cohort (n = 81). Real-time PCR was performed to assess whether there were corresponding alterations in gene expression in the adipose tissue. Results: Lower UC methylation of CpG5 was associated with higher total fat mass at 4 years (p = 0.031), total fat mass at 6–7 years (p = 0.0001) and {\%} fat mass at 6–7 years (p = 0.004). Lower UC methylation of CpG5 was also associated with higher triceps skinfold thickness at birth (p = 0.013), 6 months (p = 0.038), 12 months (p = 0.062), 2 years (p = 0.0003), 3 years (p = 0.00004) and 6–7 years (p = 0.013). Higher maternal pregnancy weight gain (p = 0.046) and lower parity (p = 0.029) were both associated with lower SLC6A4 CpG5 methylation. In adolescents, lower methylation of CpG5 in peripheral blood was associated with greater concurrent measures of adiposity including BMI (p ≤ 0.001), waist circumference (p = 0.011), subcutaneous fat (p ≤ 0.001) and subscapular, abdominal and suprailiac skinfold thicknesses (p = 0.002, p = 0.008, p = 0.004, respectively). In adipose tissue, methylation of both SLC6A4 CpG5 (p = 0.019) and expression of SLC6A4 (p = 0.008) was lower in obese compared with lean adults. Conclusions: These data suggest that altered methylation of CpG loci within SLC6A4 may provide a robust marker of adiposity across the life course.",
author = "{EpiGen Consortium} and Lillycrop, {Karen A.} and Garratt, {Emma S.} and Philip Titcombe and Melton, {Phillip E.} and Murray, {Robert J.S.} and Barton, {Sheila J.} and Rebecca Clarke-Harris and Costello, {Paula M.} and Holbrook, {Joanna D.} and Hopkins, {James C.} and Childs, {Caroline E.} and Carolina Paras-Chavez and Calder, {Philip C.} and Mori, {Trevor A.} and Lawrie Beilin and Burdge, {Graham C.} and Gluckman, {Peter D.} and Inskip, {Hazel M.} and Harvey, {Nicholas C.} and Hanson, {Mark A.} and Huang, {Rae Chi} and Cyrus Cooper and Godfrey, {Keith M.}",
year = "2019",
month = "5",
doi = "10.1038/s41366-018-0254-3",
language = "English",
volume = "43",
pages = "974--988",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Nature Publishing Group - Macmillan Publishers",
number = "5",

}

Differential SLC6A4 methylation : a predictive epigenetic marker of adiposity from birth to adulthood. / EpiGen Consortium.

In: International Journal of Obesity, Vol. 43, No. 5, 05.2019, p. 974-988.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Differential SLC6A4 methylation

T2 - a predictive epigenetic marker of adiposity from birth to adulthood

AU - EpiGen Consortium

AU - Lillycrop, Karen A.

AU - Garratt, Emma S.

AU - Titcombe, Philip

AU - Melton, Phillip E.

AU - Murray, Robert J.S.

AU - Barton, Sheila J.

AU - Clarke-Harris, Rebecca

AU - Costello, Paula M.

AU - Holbrook, Joanna D.

AU - Hopkins, James C.

AU - Childs, Caroline E.

AU - Paras-Chavez, Carolina

AU - Calder, Philip C.

AU - Mori, Trevor A.

AU - Beilin, Lawrie

AU - Burdge, Graham C.

AU - Gluckman, Peter D.

AU - Inskip, Hazel M.

AU - Harvey, Nicholas C.

AU - Hanson, Mark A.

AU - Huang, Rae Chi

AU - Cooper, Cyrus

AU - Godfrey, Keith M.

PY - 2019/5

Y1 - 2019/5

N2 - Background: The early life environment may influence susceptibility to obesity and metabolic disease in later life through epigenetic processes. SLC6A4 is an important mediator of serotonin bioavailability, and has a key role in energy balance. We tested the hypothesis that methylation of the SLC6A4 gene predicts adiposity across the life course. Methods: DNA methylation at 5 CpGs within the SLC6A4 gene identified from a previous methyl binding domain array was measured by pyrosequencing. We measured DNA methylation in umbilical cord (UC) from children in the Southampton Women’s Survey cohort (n = 680), in peripheral blood from adolescents in the Western Australian Pregnancy Cohort Study (n = 812), and in adipose tissue from lean and obese adults from the UK BIOCLAIMS cohort (n = 81). Real-time PCR was performed to assess whether there were corresponding alterations in gene expression in the adipose tissue. Results: Lower UC methylation of CpG5 was associated with higher total fat mass at 4 years (p = 0.031), total fat mass at 6–7 years (p = 0.0001) and % fat mass at 6–7 years (p = 0.004). Lower UC methylation of CpG5 was also associated with higher triceps skinfold thickness at birth (p = 0.013), 6 months (p = 0.038), 12 months (p = 0.062), 2 years (p = 0.0003), 3 years (p = 0.00004) and 6–7 years (p = 0.013). Higher maternal pregnancy weight gain (p = 0.046) and lower parity (p = 0.029) were both associated with lower SLC6A4 CpG5 methylation. In adolescents, lower methylation of CpG5 in peripheral blood was associated with greater concurrent measures of adiposity including BMI (p ≤ 0.001), waist circumference (p = 0.011), subcutaneous fat (p ≤ 0.001) and subscapular, abdominal and suprailiac skinfold thicknesses (p = 0.002, p = 0.008, p = 0.004, respectively). In adipose tissue, methylation of both SLC6A4 CpG5 (p = 0.019) and expression of SLC6A4 (p = 0.008) was lower in obese compared with lean adults. Conclusions: These data suggest that altered methylation of CpG loci within SLC6A4 may provide a robust marker of adiposity across the life course.

AB - Background: The early life environment may influence susceptibility to obesity and metabolic disease in later life through epigenetic processes. SLC6A4 is an important mediator of serotonin bioavailability, and has a key role in energy balance. We tested the hypothesis that methylation of the SLC6A4 gene predicts adiposity across the life course. Methods: DNA methylation at 5 CpGs within the SLC6A4 gene identified from a previous methyl binding domain array was measured by pyrosequencing. We measured DNA methylation in umbilical cord (UC) from children in the Southampton Women’s Survey cohort (n = 680), in peripheral blood from adolescents in the Western Australian Pregnancy Cohort Study (n = 812), and in adipose tissue from lean and obese adults from the UK BIOCLAIMS cohort (n = 81). Real-time PCR was performed to assess whether there were corresponding alterations in gene expression in the adipose tissue. Results: Lower UC methylation of CpG5 was associated with higher total fat mass at 4 years (p = 0.031), total fat mass at 6–7 years (p = 0.0001) and % fat mass at 6–7 years (p = 0.004). Lower UC methylation of CpG5 was also associated with higher triceps skinfold thickness at birth (p = 0.013), 6 months (p = 0.038), 12 months (p = 0.062), 2 years (p = 0.0003), 3 years (p = 0.00004) and 6–7 years (p = 0.013). Higher maternal pregnancy weight gain (p = 0.046) and lower parity (p = 0.029) were both associated with lower SLC6A4 CpG5 methylation. In adolescents, lower methylation of CpG5 in peripheral blood was associated with greater concurrent measures of adiposity including BMI (p ≤ 0.001), waist circumference (p = 0.011), subcutaneous fat (p ≤ 0.001) and subscapular, abdominal and suprailiac skinfold thicknesses (p = 0.002, p = 0.008, p = 0.004, respectively). In adipose tissue, methylation of both SLC6A4 CpG5 (p = 0.019) and expression of SLC6A4 (p = 0.008) was lower in obese compared with lean adults. Conclusions: These data suggest that altered methylation of CpG loci within SLC6A4 may provide a robust marker of adiposity across the life course.

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U2 - 10.1038/s41366-018-0254-3

DO - 10.1038/s41366-018-0254-3

M3 - Article

VL - 43

SP - 974

EP - 988

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

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ER -