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Blood-based DNA methylation captures variance in adult height.

Alesha A Hatton1, Robert F Hillary2, Daniel L McCartney2

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DNA methylation (DNAm) captures significant variation in adult height, jointly explaining over 80% with genetic effects. This highlights the importance of epigenomic methods beyond traditional genetic studies for complex traits.

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DNA methylationHeightMethylation profile score

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Area of Science:

  • Epigenetics
  • Human Genetics
  • Complex Trait Analysis

Background:

  • Adult height is highly heritable, yet previous studies suggested limited contribution from DNA methylation (DNAm).
  • Investigating DNAm's role in height variation is crucial for understanding complex trait etiology.

Purpose of the Study:

  • To quantify the proportion of phenotypic variation in adult height explained by genome-wide DNA methylation.
  • To assess the predictive capability of a DNA methylation profile score (MPS) for height.

Main Methods:

  • Utilized genome-wide DNAm data from 7,654 individuals in the Generation Scotland cohort.
  • Employed Bayesian penalized regression (BayesR+) to estimate DNAm probe effects.
  • Constructed a Methylation Profile Score (MPS) and validated it in independent cohorts.

Main Results:

  • Genome-wide DNAm explained 25.0% of height variation, conditional on genetic effects.
  • Joint effects of DNAm and genetics explained 80.3% of height variation.
  • The MPS showed a weak correlation with measured height (0.14-0.26) and associated with height-related health and lifestyle factors.

Conclusions:

  • Whole-genome epigenomic methods are essential for accurately assessing DNAm's contribution to complex traits.
  • Caution is advised against assuming "null traits" based solely on methylome-wide association studies.
  • Epigenetic variation plays a more substantial role in complex traits than previously assumed.