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Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP , ZNF800 , KLHL31 , and ACTL9 , and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry ( P = 2 × 10 -16 , n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity., (© 2020 by the American Diabetes Association.)

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10 -7 ). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r 2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10 -4 ) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels., (Copyright © 2019 American Society of Human Genetics. All rights reserved.)

Objective: To determine the presence of bias on the estimation of the consumption sometime in life of alcohol, tobacco or illegal drugs and inhalable substances, and to propose a correction for this in the case it is present., Materials and Methods: Mexican National Addictions Surveys (NAS) 2002, 2008, and 2011 were analyzed to compare population estimations of consumption sometime in life of tobacco, alcohol or illegal drugs and inhalable substances. A couple of alternative approaches for bias correction were developed., Results: Estimated national prevalences of consumption sometime in life of alcohol and tobacco in the NAS 2008 are not plausible. There was no evidence of bias on the consumption sometime in life of illegal drugs and inhalable substances. New estimations for tobacco and alcohol consumption sometime in life were made, which resulted in plausible values when compared to other data available., Conclusion: Future analyses regarding tobacco and alcohol using NAS 2008 data will have to rely on these newly generated data weights, that are able to reproduce the new (plausible) estimations.