Context Rare partial/complete loss-of-function mutations in the melanocortin-4 receptor (MC4R) gene are the most common cause of Mendelian obesity in European populations, but their contribution to obesity in the Mexican population is unclear. Objective and Design We investigated whether deleterious mutations in MC4R contribute to obesity in Mexican children and adults. Results We provide evidence that the MC4R p.Ile269Asn (rs79783591) mutation may have arisen in modern human populations from a founder event in native Mexicans. The MC4R Isoleucine 269 is perfectly conserved across 184 species, which suggests a critical role for the amino acid in MC4R activity. Four in silico tools (SIFT, PolyPhen-2, CADD, MutPred2) predicted a deleterious impact of the p.Ile269Asn substitution on MC4R function. The MC4R p.Ile269Asn mutation was associated with childhood (Ncontrols = 952, Ncases = 661, odds ratio (OR) = 3.06, 95% confidence interval (95%CI) [1.94–4.85]) and adult obesity (Ncontrols = 1445, Ncases = 2,487, OR = 2.58, 95%CI [1.52–4.39]). The frequency of the MC4R p.Ile269Asn mutation ranged from 0.52 to 0.59% and 1.53 to 1.59% in children and adults with normal weight and obesity, respectively. The MC4R p.Ile269Asn mutation co-segregated perfectly with obesity in 5 multigenerational Mexican pedigrees. While adults with obesity carrying the p.Ile269Asn mutation had higher BMI values than noncarriers, this trend was not observed in children. The MC4R p.Ile269Asn mutation accounted for a population attributable risk of 1.28% and 0.68% for childhood and adult obesity, respectively, in the Mexican population. Conclusion The MC4R p.Ile269Asn mutation may have emerged as a founder mutation in native Mexicans and is associated with childhood and adult obesity in the modern Mexican population.
In the two weeks after the U.S. Congress passed a package of anti-sex trafficking bills on March 21, 2018, two of the largest online commercial sex advertising platforms ceased operation. On March 23, Craigslist voluntarily removed their personals section, which had been dominated by advertisements for commercial sex. And on April 6, the Department of Justice seized Backpage.com, the largest online platform for commercial sex advertisements. Our research examines the impact of these shutdowns on a variety of important outcome variables, notably prostitution arrests and violence against women—variables that the prior literature has shown were impacted by the introduction of commercial sex advertising platforms. We employ a generalized difference-in-differences model by exploiting cross-city variation in the preshutdown usage of the two shuttered sites. We find no causal effect of the shutdowns on any of the outcome variables we measure. Further analysis suggests that these null results are likely due to the fluidity of online markets. Our data show that the majority of advertisers and users of Backpage and Craigslist’s personals quickly moved to other (often off-shore) commercial sex advertising portals. Our results highlight the challenges that governments face in reducing online sex trafficking, as the market for commercial sex advertising appears agile enough to quickly disperse to offshore sites after a few popular domestic sites are shut down. Our results have general implications for the governance of other illegal activities online. This paper was accepted by D. J. Wu, information systems.
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