In this study, we show that 4 out of 14 parameters of impulsive behaviors were significantly associated with BMI. These include parameters from all three major domains: impulsive choice, impulsive action, and impulsive personality traits. Associations were detected with delay discounting of future rewards, behavioral inhibition measured by Conner’s continuous performance test, and negative urgency, reflecting a person’s proneness to act out during periods of negative affect. All parameters were related to BMI such that more impulsivity was associated with higher BMI. We also show that the FTO rs3751812 minor allele T is positively associated with BMI and negatively associated with 2 impulsive personality traits (lack of premeditation and lack of perseverance), independently of BMI. The association between rs3751812 and BMI survives after adjusting for lack of premeditation, but not for lack of perseverance or both for lack of perseverance and lack of premeditation.

The associations between several impulsivity domains and BMI have been previously reported in the literature. Amlung and colleagues reported a meta-analysis of 39 independent studies showing a positive association between delay discounting of food and money and obesity9. Furthermore, cross-sectional and longitudinal studies linking BMI and reward responsiveness, sensation seeking, lack of perseverance, lack of premeditation, positive and negative urgency have been reported in children and adults from Europe and the US8,18,19,20,21.

Factors such as age, sex, food addiction, and genetics have been shown to mitigate the association between impulsivity and BMI8,13,19,20. Our study reports an association between rs3751812 and BMI in US university students of European ancestry. This association is plausible, as (i) Universities in North America represent an obesity-prone environment for young adults22; (ii) SNPs in FTO are strongly associated with polygenic obesity in children and adults of European descent23; (iii) SNPs in FTO interact with obesity-prone environments to promote obesity24; (iv) an association between weight gain and FTO rs9939609 SNP (in strong linkage disequilibrium with rs3751812 in populations of European ancestry) has been previously reported in university students from the United Kingdom25.

The FTO rs3751812 obesity risk T allele is also negatively associated with lack of premeditation and lack of perseverance in our study. In 697 US adults of European ancestry followed for up to 23 years, rs1421085 C minor allele showed an association with increased BMI and reduced medial prefrontal cortical function during aging16. Consistent with reduced brain function in regions intrinsic to impulse control and taste responsiveness, rs1421085 C allele carriers exhibited increased excitement seeking and intake of fatty foods16. Of note, rs1421085 is in perfect linkage disequilibrium with rs3751812 in the five ethnic groups from the 1000 Genomes Project. In contrast, Jonassaint and colleagues did not find any association between FTO SNPs and the cognitive, motor and non-planning components of the Barratt impulsivity scales in 1 085 and 677 females of European descent with anorexia nervosa and healthy weight control, respectively15. While more studies are needed to understand the precise contribution of FTO SNPs to impulsive behaviors, additional lines of evidences in the literature make the association biologically relevant. SNPs in intron 1 of FTO have been associated with differences of methylation and expression of FTO in blood and neurons, respectively26,27. FTO is a nucleic acid demethylase and is highly expressed in the brain28. Loss-of-function mutations in FTO result in an autosomal-recessive lethal syndrome characterized by growth retardation, microcephaly, severe psychomotor delay, functional brain deficits, and facial dysmorphism29. BMI-increasing alleles in FTO have been associated with lower brain, cortical gray matter, and nucleus accumbens volumes, reduced activity in brain areas important for emotion, impulse control and reward responsiveness, structural brain atrophy, reduced verbal fluency, increased loss of control episodes over eating, and decreased risk of stress/nervousness, alcohol dependence, depression, and suicide30. SNPs in intron 1 of FTO also regulate the expression of other important genes in the regulation of body weight (e.g. RPGRIP1L, IRX3) in neurons26,31,32,33. Considering the important role of RPGRIP1L in cilium function26,31, and the critical link between cilium function, hyperphagic obesity and cognition (e.g. Bardet-Biedl syndrome)34, it is tempting to speculate that changes in brain expression of RPGRIP1L induced by FTO SNPs may also have an impact on impulsive behaviors.

Adjustment for BMI did not remove the association between rs3751812 and lack of perseverance and premeditation, suggesting that the SNP may directly influence impulsive behaviors independent of BMI. In contrast, the association between rs3751812 and BMI disappeared after adjusting for lack of perseverance or lack of perseverance and premeditation parameters together. These results suggest that the association between FTO and BMI may involve changes in impulsive behaviors.

It is important to note that the 4 impulsivity traits associated with BMI differ from the two impulsive personality traits associated with rs3751812 SNP in our study. Moreover, impulsivity traits are positively associated with BMI, whereas rs3751812 T allele is associated with decreased impulsivity and increased BMI. A possible explanation for these counterintuitive observations is because FTO is involved in a specific molecular pathway28, while the association between BMI and impulsivity is an integration of all genetic and environmental influences linking both traits. Consistent with this view is the recent demonstration that the impulsivity trait delay discounting shares a substantial genetic overlap with BMI in populations of European ancestry (r g = 0.18 ± 0.08, P = 8.9 × 10−3)13. These data suggest the involvement of multiple genes in linking impulsive behaviors to obesity. SNPs in FTO account for 1% of BMI variation in European populations30, and may represent as such one of the many genetic determinants linking the association between impulsivity traits and BMI9,20,35. Our data suggests that FTO SNPs may have a pleiotropic/BMI-independent association with two impulsivity traits (lack of perseverance and lack of premeditation). Supporting this hypothesis is recent evidence of a BMI-independent association between FTO SNPs and brain aging markers30,36.

This study has several strengths. It addresses a controversy caused by two inconsistent studies that have investigated the association of FTO SNPs with impulsivity15,16. In addition, we provide accurate measurements of BMI and very detailed assessments of the multidimensional construct of impulsivity. Finally, our study includes original analyses to model the pattern of association between FTO SNP, impulsivity and BMI. We also acknowledge that the current research has limitations. Our sample is modest by the standards of genetic association studies and focuses predominantly on US university students of European descent, limiting our ability to generalize our results to other populations. Another limitation is that our study is not longitudinal. The cross-sectional nature of this study precludes causal inferences to be made about the association between impulsivity traits and BMI. Finally, only one obesity SNP (FTO rs3751812) was studied, but there are now more than 940 independent SNPs that have been convincingly associated with BMI/obesity in recent literature14. Studying the association of a polygenic obesity risk score with impulsivity traits represents an exciting direction of research.

In conclusion, our observational and genetic data indicate a complex pattern of association between impulsive behaviors and BMI in healthy young American-European adults. More research is needed to precise the contribution of SNPs in FTO and other obesity genes to impulsive behaviors in diverse ethnicities. Mendelian randomization studies are also warranted to evidence the causal nature of the association between impulsive behaviors and susceptibility to obesity.