Abstract
The A allele of rs9939609 in the FTO gene predisposes to increased body mass index (BMI) and obesity. Recently we showed an inverse association between the obesity related A allele of rs9939609 and alcohol dependence which was replicated by others. Since this finding raises a possibility that FTO may be associated with other psychiatric phenotypes, we aimed to examine association of rs9939609 with completed suicide. We genotyped rs9939609 in 912 suicide victims and 733 controls using TaqMan approach. We observed an inverse association between suicide and the rs9939609 A allele (OR = 0.80, P = 0.002, Pcor = 0.006) with genotype distribution suggesting a co-dominant effect. Given the link between alcoholism and suicide under influence of alcohol reported in Polish population, confounding by alcohol addiction was unlikely due to apparently similar effect size among cases who were under influence of ethanol at the time of death (OR = 0.76, P = 0.003, N = 361) and those who were not (OR = 0.80, P = 0.007, N = 469). The search for genotype-phenotype correlations did not show significant results. In conclusion, our study proves that there is an inverse association between rs9939609 polymorphism in FTO gene and completed suicide which is independent from association between FTO and alcohol addiction.
Highlights
The FTO gene and the A allele of rs9939609 polymorphism is known for association with body mass index (BMI), obesity risk, and type 2 diabetes [1], which has been confirmed in a Polish population [2] as well as in a recent multiethnic study including over 170 000 individuals [3]
The major novel finding in our study is the inverse association between the obesity associated A allele of rs9939609 in the FTO gene and completed suicide
If our results were secondary to the described link between FTO variants and alcoholism such an association could be expected as we have previously shown that in Polish population alcoholism and suicide under influence of alcohol frequently co-occur [19]
Summary
The FTO gene and the A allele of rs9939609 polymorphism is known for association with body mass index (BMI), obesity risk, and type 2 diabetes [1], which has been confirmed in a Polish population [2] as well as in a recent multiethnic study including over 170 000 individuals [3].The exact function of FTO gene, mainly expressed in several brain regions [4] including pineal, prefrontal cortex, hypothalamus and amygdala (http://biogps.org/), is not known. A recent study has shown that FTO rs9939609 A variant, which predisposes to obesity, has a protective effect on depression [13]. Our previous study showed a link between the FTO gene and alcohol drinking habits among general population as well as an inverse association of the obesity associated variant with alcohol dependence [2]. This protective effect of FTO variants on alcoholism has been confirmed by independent studies in other populations [15,16]
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