Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Effect of calcium and dairy foods in high protein, energy-restricted diets on weight loss and metabolic parameters in overweight adults

ObjectiveTo compare the effects two high-protein (HP) diets that differ in dietary calcium and protein source on weight loss, body composition, glucose and lipid metabolism, markers of liver function, fibrinolysis and endothelial function and blood pressure.DesignRandomized, parallel study (12 wk of energy restriction, 4 wk of energy balance) of high dairy protein/high-calcium (DP, 2400 mg Ca/d) and high mixed protein/moderate calcium (MP, 500 mg Ca/d) diets (5.5 MJ/d, 34% protein, 41% carbohydrate, 24% fat).SubjectsIn all, 50 healthy, overweight (age 25-64 y; body mass index 25-35 kg/m(2);) males (n=20) and females (n=30).ResultsLoss of total weight (-9.7+/-3.8 kg), fat mass (-8.3+/-0.4 kg) and lean mass (-1.6+/-0.3 kg) were independent of dietary group. Improvements in fasting insulin, lipids, systolic/diastolic blood pressure, and markers of liver function, fibrinolysis and endothelial function were independent of dietary intervention.ConclusionsIncreased dietary calcium/dairy foods in an energy-restricted, HP diet does not affect weight loss or body composition. Weight reduction following increased protein diets is associated with beneficial metabolic outcomes that are not affected by protein source