rs1108086 — FTO FTO Intron 8 T>C

An FTO intron-8 variant in the same haplotype block as rs1420318, with emerging associations with bone mineral density and alcohol dependence susceptibility; distinct from the primary intron-1 obesity cluster

See your personal result for FTO

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

FTO Intron 8: A Distinct Variant at the Obesity Gene Locus

The FTO (fat mass and obesity-associated) gene spans more than 400 kilobases on chromosome 16, containing nine exons and multiple functionally distinct intronic regions. The well-known FTO obesity signal resides in intron 1 (rs9939609, rs1421085), but rs1108086 sits in a completely different part of the gene — intron 811 intron 8
The eighth non-coding interval in the FTO pre-mRNA, approximately 100 kb downstream of the primary obesity cluster at chromosome 16 position 54,066,457 (GRCh38). The two regions are in very low linkage disequilibrium22 very low linkage disequilibrium
r² ≈ 0.11 in CEU populations — knowing your rs1108086 genotype tells you almost nothing about your rs9939609 genotype, making this an essentially independent locus within the same gene.

rs1108086 is in very high LD with rs1420318 (r² = 0.953 in Europeans), meaning both variants tag the same intron-8 haplotype. Carriers of the C allele at rs1108086 almost certainly carry the corresponding A allele at rs1420318, and vice versa — the two variants represent the same underlying functional signal.

The Evidence

Published evidence for this locus comes from two independent research programs. The first involves bone mineral density (BMD)33 bone mineral density (BMD)
A measure of bone mass used to assess fracture risk and diagnose osteoporosis. A 2011 study by Guo et al. tested 141 FTO SNPs for BMD associations in two Chinese Han cohorts (N=818 and N=809) and one Caucasian cohort (N=2,286). In Chinese populations, six intron-8 FTO SNPs — all in high mutual LD and including the same haplotype block as rs1108086 — showed significant associations with hip BMD (combined p = 1.47×10⁻⁴ to 4.99×10⁻⁴), with each minor allele copy associated with increased hip BMD (β ≈ 0.015–0.025). In the Caucasian sample, the proxy variant rs1420318 showed a nominal association with spine BMD (p = 6.14×10⁻³). These associations are biologically plausible: FTO is an m6A RNA demethylase44 m6A RNA demethylase
Removes N6-methyladenosine modifications from mRNA to regulate gene expression expressed in osteoblast-rich tissues, and body weight (modulated by the intron-1 variants) is itself a major determinant of bone loading.

The second line of evidence comes from a 2013 study by Wang et al.55 2013 study by Wang et al.
Genetic variants in the fat mass- and obesity-associated (FTO) gene are associated with alcohol dependence. Journal of Molecular Neuroscience that screened 167 FTO SNPs across two Caucasian samples (COGA: 660 cases/400 controls; SAGE: 623 cases/1,016 controls). rs1108086 ranked among the top three FTO SNPs associated with alcohol dependence in the SAGE cohort (p = 0.00086). This finding resonates with FTO's broader role in appetite and reward circuitry beyond adiposity alone — FTO is highly expressed in hypothalamic neurons and modulates dopaminergic signaling pathways relevant to substance use as well as eating behavior.

Both associations remain emerging66 emerging
Neither reached genome-wide significance (p < 5×10⁻⁸), and neither has been independently replicated in multiple large cohorts at this specific locus. The BMD association was stronger in Chinese than in Caucasian populations, and the alcohol signal appeared in one of two studied cohorts.

Practical Implications

The intron-8 locus does not participate in the IRX3/IRX5 thermogenesis mechanism that drives FTO's obesity association. Carriers of the C allele at rs1108086 do not have the beige-to-white adipocyte shift associated with the intron-1 cluster. Instead, the available evidence points toward two distinct areas: bone mineral density monitoring (particularly hip and spine BMD, where the intron-8 signal was detected) and awareness of alcohol susceptibility signals. The C allele is particularly common in African and South Asian ancestry groups (~49% and ~41% respectively), compared to only ~13% in Europeans.

Interactions

rs1108086 and rs1420318 are near-redundant tags for the same intron-8 haplotype (r² = 0.953 in Europeans). They should not both generate independent compound actions — users who match one almost certainly match the other. By contrast, rs1108086 and the intron-1 obesity variants (rs9939609, rs1421085) are in low LD (r² ≈ 0.11) and can be independently inherited, representing additive effects at different functional regions of FTO.

Genotype Interpretations

What each possible genotype means for this variant.

TT Common Genotype Normal

Reference genotype — no elevated risk at this FTO intron-8 position

You carry two copies of the T allele, the reference sequence at this FTO intron-8 position (chromosome 16, GRCh38). Approximately 76% of people of European ancestry share this genotype. The available evidence for this locus does not associate the TT genotype with elevated bone density or alcohol dependence risk.

CT One C Allele Intermediate

One copy of the FTO intron-8 C allele — emerging association with bone density and alcohol susceptibility

rs1108086 is in very high LD with rs1420318 (r² = 0.953 in Europeans), meaning the two variants tag the same underlying intron-8 haplotype. The bone density signal from Guo et al. 2011 was stronger in Chinese populations for hip BMD, with nominal spine BMD association in Caucasians. The alcohol dependence signal from Wang et al. 2013 was observed in one cohort (SAGE) but requires replication. Both findings should be treated as advisory signals that warrant monitoring, not as established clinical risk factors. The intron-8 haplotype is not in meaningful LD with the intron-1 obesity cluster, so this locus does not contribute to FTO's established thermogenic or adiposity effects.

CC Two C Alleles High Risk

Homozygous for the FTO intron-8 C allele — full additive dosage for emerging bone density and alcohol susceptibility signals

CC homozygotes at rs1108086 carry the maximum copy number of the intron-8 C allele and, by extension (r² = 0.953), the corresponding rs1420318 A allele haplotype. The studies that identified this signal (Guo et al. 2011 for BMD, Wang et al. 2013 for alcohol dependence) did not report separate CC-specific effect estimates, in part because this genotype is rare in European-ancestry cohorts. The additive architecture means CC homozygotes would be expected to show larger effects than TC heterozygotes if the associations are real and additive. The intron-8 haplotype is independent of FTO's intron-1 obesity cluster, so this genotype does not imply elevated thermogenesis-related body composition risk from this locus.