Publisher Correction: Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.

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Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.

Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.

Genome-wide association analysis identifies 13 new risk loci for schizophrenia.

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Y-chromosomal evidence of the cultural diffusion of agriculture in Southeast Europe.

The debate concerning the mechanisms underlying the prehistoric spread of farming to Southeast Europe is framed around the opposing roles of population movement and cultural diffusion. To investigate the possible involvement of local people during the transition of agriculture in the Balkans, we analysed patterns of Y-chromosome diversity in 1206 subjects from 17 population samples, mainly from Southeast Europe. Evidence from three Y-chromosome lineages, I-M423, E-V13 and J-M241, make it possible to distinguish between Holocene Mesolithic forager and subsequent Neolithic range expansions from the eastern Sahara and the Near East, respectively. In particular, whereas the Balkan microsatellite variation associated to J-M241 correlates with the Neolithic period, those related to E-V13 and I-M423 Balkan Y chromosomes are consistent with a late Mesolithic time frame. In addition, the low frequency and variance associated to I-M423 and E-V13 in Anatolia and the Middle East, support an European Mesolithic origin of these two clades. Thus, these Balkan Mesolithic foragers with their own autochthonous genetic signatures, were destined to become the earliest to adopt farming, when it was subsequently introduced by a cadre of migrating farmers from the Near East. These initial local converted farmers became the principal agents spreading this economy using maritime leapfrog colonization strategies in the Adriatic and transmitting the Neolithic cultural package to other adjacent Mesolithic populations. The ensuing range expansions of E-V13 and I-M423 parallel in space and time the diffusion of Neolithic Impressed Ware, thereby supporting a case of cultural diffusion using genetic evidence.