In the cross-trait meta-analyses, we identified (1) 14 genetic loci (including NEGR1, CADM2, PMAIP1, PARK2) that are associated with both obesity and SSRIs treatment response; (2) five genetic loci (LINC01412, PHACTR1, CDKN2B, ATXN2, KCNE2) with effects on CAD and SSRIs treatment response.
Human Ataxin-2 (ATXN2) gene locus variants have been associated with obesity, diabetes mellitus type 1,and hypertension in genome-wide association studies, whereas mouse studies showed the knock-out of Atxn2 to lead to obesity, insulin resistance, and dyslipidemia.
Mouse lines deficient for atxn2 develop marked hyperphagia and obesity raising the possibility that loss-of-function mutations in the ATXN2 gene may be related to energy balance in humans.
Interestingly, polyphagia and obesity were striking manifestations in the middle stage of the disease; an observation that might support a previously suggested relation between the ataxin-2 gene and body weight.