r-project.org, Amin et al. 2007). A meta-analysis was performed using METAL (http://www.sph.umich.edu/csg/abecasis/metal/). Study specific P-values and effect directions were converted into a Z-statistics and
weighted with sample size of each study. Results Association analysis in Sorbs An association analysis for variant rs2237781 located in intron 4 of GRM8 was performed in the discovery population. Using linear regression analysis and an additive inheritance model the major G allele was significantly associated with higher restraint in eating chemical structure behavior (adjusted P = 1.9 × 10−4) in the Sorbs (Table (Table2).2). No significant association could be detected for the eating behavior factors disinhibition Inhibitors,research,lifescience,medical and susceptibility to hunger feelings. Given a low frequency of the A allele (minor allele frequency [MAF 0.07]) we also included a recessive model of inheritance which showed significantly higher restraint values in homozygous G allele carriers (Table (Table22). Table 2 Association analysis for rs2237781 with eating behavior Inhibitors,research,lifescience,medical factors under linear regression analyses When analyzing Inhibitors,research,lifescience,medical data regarding alcohol intake, smoking behavior, and coffee consumption, we detected a higher but nonsignificant intake for each category in homozygous G allele carriers (Table (Table22). Association analysis in German cohort
In our second cohort comprising a limited sample set of Inhibitors,research,lifescience,medical 293 individuals we observed no significant association (Table (Table2).2). However, we detected the same effect direction between the major G allele as the allele show tendency for higher restraint values (Table (Table2).2). No significant association was detected for the eating behavior factors disinhibition and susceptibility to hunger feelings. Association analysis in Old Order Amish Despite consistent effect directions with the discovery and the German cohort, no significant association was found between rs10487466 Inhibitors,research,lifescience,medical and restraint eating behavior in the Amish using linear regression models (adjusted P = 0.908, β = +0.096; Table Table3).3). Of note, there
was a significant association of rs10487466 with hunger (P = 3.9 × 10−3, adjusted for age, sex, and family structure, data not shown). Nature Medicine Table 3 Meta-analysis for association of rs2237781 with restraint including Sorbs, German cohort, and Old Order Amish Meta-analysis including all three study populations A sample size weighted meta-analysis including the results from all three study populations (Sorbs, German cohort, and Old Order Amish) resulted in a significant association for restraint (combined P = 3.1 × 10−3, Z-score 2.948, Table Table33). Discussion The metabotropic receptor GRM8 has been associated with smoking behavior (Vink et al. 2009) and liability to alcoholism (Chen et al. 2009) implying there may be a role in addiction vulnerability.