Hormonal
The FTO obesity susceptibility haplotype (tagged by rs8050136 risk allele A) is associated with increased DNA methylation levels within a 7.7 kb region containing a long-range enhancer for IRX3, driven by CpG-creating SNPs.
This research highlights that carrying the FTO risk variant is linked to higher methylation in a region that regulates the IRX3 gene, which is involved in energy balance. While this is a biological mechanism rather than a lifestyle tip, it suggests that the risk allele's effect might be mediated through gene regulation (epigenetics) rather than just protein function. This implies that environmental factors influencing methylation could theoretically interact with this genetic risk.
we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.4061024, permutation p = 1.061023)... This 7.7 kb region of haplotype-specific methylation (HSM), encapsulates a Highly Conserved Non-Coding Element (HCNE) that has previously been validated as a long-range enhancer
Why this rating
Strong statistical significance (p < 10^-24) and validation via pyrosequencing in multiple tissues (blood, brain), though sample size for tissue replication was small (n=14).
Source
Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus
Christopher G. Bell et al. · PLoS ONE · 2010
DOI 10.1371/journal.pone.0014040
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