RESUMO
Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
Assuntos
Antropometria/métodos , Pesos e Medidas Corporais , Estudo de Associação Genômica Ampla , Caracteres Sexuais , Estatura/genética , Índice de Massa Corporal , Peso Corporal/genética , Feminino , Loci Gênicos , Genoma Humano , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Circunferência da Cintura/genética , Relação Cintura-QuadrilRESUMO
Following one or more chemotherapy treatments, many patients report that they experience anticipatory nausea. This phase of nausea has been interpreted as a classically conditioned response where a conditional association develops between the contextual clinic cues and the nausea and/or vomiting that developed following treatment. Although rats do not vomit, they display a distinctive gaping reaction when exposed a flavored solution previously paired with a toxin. Here we report that, even in the absence of a flavored solution, rats display conditioned gaping reactions during exposure to a distinctive context previously paired with a high dose of lithium (Experiment 1 with a distinctive odor and Experiment 3 without a distinctive odor), a low dose of lithium (Experiment 2) or provocative vestibular stimulation (Experiment 2). These results suggest that the conditioned gaping reaction in rats is selectively elicited by nausea-paired contextual stimuli, as well as flavors. This rat model of anticipatory nausea may serve as a valuable preclinical tool to evaluate the effectiveness of anti-nausea treatments and the side effect of nausea produced by newly developed pharmaceutical compounds intended for other clinical treatments.