Comparative population genomics reveals genetic basis underlying body size of domestic chickens.

Body size is the most important economic trait for animal production and breeding. Several hundreds of loci have been reported to be associated with growth trait and body weight in chickens. The loci are mapped to large genomic regions due to the low density and limited number of genetic markers in previous studies. Herein, we employed comparative population genomics to identify genetic basis underlying the small body size of Yuanbao chicken (a famous ornamental chicken) based on 89 whole genomes. The most significant signal was mapped to the BMP10 gene, whose expression was upregulated in the Yuanbao chicken. Overexpression of BMP10 induced a significant decrease in body length by inhibiting angiogenic vessel development in zebrafish. In addition, three other loci on chromosomes 1, 2, and 24 were also identified to be potentially involved in the development of body size. Our results provide a paradigm shift in identification of novel loci controlling body size variation, availing a fast and efficient strategy. These loci, particularly BMP10, add insights into ongoing research of the evolution of body size under artificial selection and have important implications for future chicken breeding.

Identification of SLC25A37 as a major depressive disorder risk gene.

Major depressive disorder (MDD) is one of the most prevalent and disabling mental disorders, but the genetic etiology remains largely unknown. We performed a meta-analysis (14,543 MDD cases and 14,856 controls) through combining the GWAS data from the Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium and the CONVERGE consortium and identified seven SNPs (four of them located in the downstream of SCL25A37) that showed suggestive associations (P < 5.0 × 10-7) with MDD. Systematic integration (Sherlock integrative analysis) of brain eQTL and GWAS meta-analysis identified SCL25A37 as a novel MDD risk gene (P = 2.22 × 10-6). A cis SNP (rs6983724, ∼28 kb downstream of SCL25A37) showed significant association with SCL25A37 expression (P = 1.19 × 10-9) and suggestive association with MDD (P = 1.65 × 10-7). We validated the significant association between rs6983724 and SCL25A37 expression in independent expression datasets. Finally, we found that SCL25A37 is significantly down-regulated in hippocampus and blood of MDD patients (P = 3.49 × 10-3 and P = 2.66 × 10-13, respectively). Our findings implicate that the SCL25A37 is a MDD susceptibility gene whose expression may influence MDD risk. The consistent down-regulation of SCL25A37 in MDD patients in three independent samples suggest that SCL25A37 may be used as a potential biomarker for MDD diagnosis. Further functional characterization of SCL25A37 may provide a potential target for future therapeutics and diagnostics.

Recent Positive Selection Drives the Expansion of a Schizophrenia Risk Nonsynonymous Variant at SLC39A8 in Europeans.

Natural selection has played important roles in optimizing complex human adaptations. However, schizophrenia poses an evolutionary paradox during human evolution, as the illness has strongly negative effects on fitness, but persists with a prevalence of ~0.5% across global populations. Recent studies have identified numerous risk variations in diverse populations, which might be able to explain the stable and high rate of schizophrenia morbidity in different cultures and regions, but the questions about why the risk alleles derived and maintained in human gene pool still remain unsolved. Here, we studied the evolutionary pattern of a schizophrenia risk variant rs13107325 (P < 5.0 × 10(-8) in Europeans) in the SLC39A8 gene. We found the SNP is monomorphic in Asians and Africans with risk (derived) T-allele totally absent, and further evolutionary analyses showed the T-allele has experienced recent positive selection in Europeans. Subsequent exploratory analyses implicated that the colder environment in Europe was the likely selective pressures, ie, when modern humans migrated "out of Africa" and moved to Europe mainland (a colder and cooler continent than Africa), new alleles derived due to positive selection and protected humans from risk of hypertension and also helped them adapt to the cold environment. The hypothesis was supported by our pleiotropic analyses with hypertension and energy intake as well as obesity in Europeans. Our data thus provides an intriguing example to illustrate a possible mechanism for maintaining schizophrenia risk alleles in the human gene pool, and further supported that schizophrenia is likely a product caused by pleiotropic effect during human evolution.