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The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Schizophrenia is a highly heritable genetic disorder, however, identification of specific genetic risk variants has proven difficult because of its complex polygenic nature—a large multi-stage genome-wide association study identifies 128 independent associations in over 100 loci (83 of which are new); key findings include identification of genes involved in glutamergic neurotransmission and support for a link between the immune system and schizophrenia.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

Here, in the first of three papers on the genetics of schizophrenia, a genome-wide association study of single nucleotide polymorphisms using data from several large genome-wide scans reveals significant associations to individual loci that implicate perturbations in immunity, brain development, memory and cognition in the predisposition to schizophrenia.

The genetics of schizophrenia and other mental disorders are complex and poorly understood, and made even harder to study due to reduced reproduction resulting in negative selection pressure on risk alleles. Two independent large-scale genome wide studies of thousands of patients and controls by two international consortia confirm a previously identified locus, but also reveal novel associations. In this study, de novo (spontaneous) copy number variants are reported on chromosomes 1 and 15.

This Comment discusses how data from smartphones or wearables could be used for behavioural phenotyping, knowledge that may help to reveal the genetic and environmental contributions to disease-related behavioural variation.

A survey of genetic variation in Native American and Siberian populations reveals that Native Americans are descended from at least three streams of gene flow from Asia: after the initial peopling of the continent there was a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America.

Cristen Willer and colleagues report genome-wide association analyses for blood lipid levels in 188,578 individuals. They identify 62 loci newly associated with blood lipid levels, refine the association signals at 12 loci and examine associations with cardiovascular and metabolic traits.

Sekar Kathiresan and colleagues examine 185 common variants using a modified mendelian randomization approach and provide evidence supporting a causal role of triglyceride-rich lipoproteins in the development of coronary artery disease.

Paul Thompson and colleagues report a genome-wide association study for hippocampal, intracranial and total brain volume. They identify a locus at 12q24 associated with hippocampal volume and a locus at 12q14 associated with intracranial volume.

Gonçalo Abecasis and colleagues report associations with fasting plasma glucose levels in a collection of ten genome–wide association scans from the MAGIC consortium. They find variants in the gene encoding melatonin receptor 1B that are associated with fasting glucose levels and, in a meta-analysis of 13 case-control studies, also show association with increased risk of type 2 diabetes.

Leena Peltonen and colleagues report a genome-wide association study of cholesterol and triglyceride levels in 16 population-based cohorts across Europe. Six new loci were identified, and overall a genetic risk score improves the screening of high risk groups for dyslipidemia.

Eleazar Eskin and colleagues report a variance component model for correcting for sample structure in association studies. The EMMAX program is publicly available and may be used for analysis of genome-wide association study datasets.

The Nordic region, comprising primarily Denmark, Estonia, Finland, Iceland, Norway and Sweden, has many of the necessary characteristics for being at the forefront of genome-based precision medicine. These include egalitarian and universal healthcare, expertly curated patient and population registries, biobanks, large population-based prospective cohorts linked to registries and biobanks, and a widely embraced sense of social responsibility that motivates public engagement in biomedical research. However, genome-based precision medicine can be achieved only through coordinated action involving all actors in the healthcare sector. Now is an opportune time to organize scientists in the Nordic region, together with other stakeholders including patient representatives, governments, pharmaceutical companies, academic institutions and funding agencies, to initiate a Nordic Precision Medicine Initiative. We present a roadmap for how this organization can be created. The Initiative should facilitate research, clinical trials and knowledge transfer to meet regional and global health challenges.

Using whole-genome data for single-nucleotide polymorphism and results from genome-wide association studies, the authors show that people’s preference for pairing with those with similar phenotypic traits has genetic causes and consequences.

Naomi Wray and colleagues report an analysis of genome-wide association data sets from the Psychiatric Genomics Consortium for five psychiatric disorders. They find that common variation explains 17–29% of the variance in liability and provide further support for a shared genetic etiology for these related psychiatric disorders.

Song et al. conduct a geospatial analysis of variations in incidence of mood and psychotic disorders and access to care in Caldas, Colombia. They show that many patients requiring only outpatient care live too far away to access it and identify hotspots of more severely ill patients, highlighting the need for targeted interventions.

As long-awaited advances in psychiatric genetics begin to materialize in force, promising to steer us safely to the best of times in psychiatric disease research, many pharmaceutical companies pull away from the challenge of drug development, threatening to bring us to the worst of times for the field. There is a real danger of missed opportunities and a sense of urgency for defining a clear path forward.

The Schizophrenia Psychiatric Genome-Wide Association Study Consortium reports five genetic loci newly associated with risk of schizophrenia, involving 17,836 cases of schizophrenia and 33,859 healthy controls. The new locus with the strongest support of association was located within an intron for microRNA 137, a known regulator of neuronal development. Four other genome-wide significant loci for schizophrenia contain predicted targets of MIR137, suggesting that disruption to pathways involving MIR137 may be an etiologic mechanism in schizophrenia.

Although humans are genetically similar, marked geographic patterns exist for many heritable traits. The investigation of spatial patterns at loci under selection can address fundamental questions about geographically variable traits in humans and give new insights into human adaptation.

What constitutes replication of a genotype–phenotype association, and how best can it be achieved?