Search

The use of spoken and written language is a capacity that is unique to humans. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30-80%, depending on the trait. The relevant genetic architecture is complex, heterogeneous, and multifactorial, and yet to be investigated with well-powered studies. Here, we present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures: word reading, nonword reading, spelling, phoneme awareness, and nonword repetition, with total sample sizes ranging from 13,633 to 33,959 participants aged 5-26 years (12,411 to 27,180 for those with European ancestry, defined by principal component analyses). We identified a genome-wide significant association with word reading (rs11208009, p=1.098 × 10−8) independent of known loci associated with intelligence or educational attainment. All five reading-/language-related traits had robust SNP-heritability estimates (0.13–0.26), and genetic correlations between them were modest to high. Using genomic structural equation modelling, we found evidence for a shared genetic factor explaining the majority of variation in word and nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence and educational attainment. A multivariate GWAS was performed to jointly analyse word and nonword reading, spelling, and phoneme awareness, maximizing power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with neuroimaging traits identified association with cortical surface area of the banks of the left superior temporal sulcus, a brain region with known links to processing of spoken and written language. Analysis of evolutionary annotations on the lineage that led to modern humans showed enriched heritability in regions depleted of Neanderthal variants. Together, these results provide new avenues for deciphering the biological underpinnings of these uniquely human traits.

Variable preferences for different foods are among the main determinants of their intake and are influenced by many factors, including genetics. Despite considerable twins’ heritability, studies aimed at uncovering food-liking genetics have focused mostly on taste receptors. Here, we present the first results of a large-scale genome-wide association study of food liking conducted on 161,625 participants from UK Biobank. Liking was assessed over 139 specific foods using a 9-point hedonic scale. After performing GWAS, we used genetic correlations coupled with structural equation modelling to create a multi-level hierarchical map of food liking. We identified three main dimensions: high caloric foods defined as “Highly palatable”, strong-tasting foods ranging from alcohol to pungent vegetables, defined as “Learned” and finally “Low caloric” foods such as fruit and vegetables. The “Highly palatable” dimension was genetically uncorrelated from the other two, suggesting that two independent processes underlie liking high reward foods and the Learned/Low caloric ones. Genetic correlation analysis with the corresponding food consumption traits revealed a high correlation, while liking showed twice the heritability compared to consumption. For example, fresh fruit liking and consumption showed a genetic correlation of 0.7 with heritabilities of 0.1 and 0.05, respectively. GWAS analysis identified 1401 significant food-liking associations located in 173 genomic loci, with only 11 near taste or olfactory receptors. Genetic correlation with morphological and functional brain data (33,224 UKB participants) uncovers associations of the three food-liking dimensions with non-overlapping, distinct brain areas and networks, suggestive of separate neural mechanisms underlying the liking dimensions. In conclusion, we created a comprehensive and data-driven map of the genetic determinants and associated neurophysiological factors of food liking beyond taste receptor genes.

Background: Ill decisions and reckless behaviors due to low self-control are concurrently and longitudinally costly, and revealing possible factors contributing to individual differences in self-control is necessary. It is hypothesized that genetically sensitivity interacts with life stressors in the prediction of the development of low self-control (gene environment interaction), yet attempts to test this hypothesis mostly concern candidate gene studies yielding inconclusive results. The goal of this research was to bring findings from large scale gene identification studies into the developmental psychology framework, taking the polygenic nature of complex traits into account. Methods: Using data of a large population-based twin sample, we tested whether polygenic risk scores for self-control problems – based on the most recent ADHD GWAS – predict self-control problems in adults, and whether this polygenic risk scores interact with the presence of environmental stressors. Results: While polygenic scores and life stressors significantly predicted low self-control, we did not find a significant interaction effect. Conclusions: Empirically, finding statistical evidence for this hypothesis remains a challenge, and more research is needed to investigate how to better detect G x E.

Following publication of this article, the authors noticed an error in Supplementary Table 1. In the original Supplementary Table 1, one of the criteria for control participants was incorrectly given as ‘Report extensive recent symptoms of depression: less than 14 on summed response (where “not at all” = 1 and “nearly every day” = 4) to recent’. This has now been corrected to: ‘Report extensive recent symptoms of depression: less than 5 on summed response (where “not at all” = 1 and “nearly every day” = 4) to recent’.

Various non-psychotic psychiatric disorders in childhood and adolescence can precede the onset of schizophrenia, but the nature of this relationship remains unclear. We investigated to what extent the association between schizophrenia and psychiatric disorders in childhood is explained by shared genetic risk factors.Polygenic risk scores (PRS), reflecting an individual’s genetic risk for schizophrenia, were constructed for participants in two birth cohorts (2,588 children from the Netherlands Twin Register (NTR) and 6,127 from the Avon Longitudinal Study of Parents And Children (ALSPAC)). The associations between schizophrenia PRS and measures of anxiety, depression, attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder/conduct disorder (ODD/CD) were estimated at age 7, 10, 12/13 and 15 years in the two cohorts. Results were then meta-analyzed, and age-effects and differences in the associations between disorders and PRS were formally tested in a meta-regression.The schizophrenia PRS was associated with childhood and adolescent psychopathology Where the association was weaker for ODD/CD at age 7. The associations increased with age this increase was steepest for ADHD and ODD/CD. The results are consistent with a common genetic etiology of schizophrenia and developmental psychopathology as well as with a stronger shared genetic etiology between schizophrenia and adolescent onset psychopathology.A multivariate meta-analysis of multiple and repeated observations enabled to optimally use the longitudinal data across diagnoses in order to provide knowledge on how childhood disorders develop into severe adult psychiatric disorders.

Several linkage studies on anxiety have been carried out in samples ascertained through probands with panic disorder. The results indicated that using a broad anxiety phenotype instead of a DSM-IV anxiety disorder diagnosis might enhance the chance of finding a linkage signal. In the current study, a genome-wide linkage analysis was performed on anxiety measured with a self-report questionnaire whose scores are highly correlated with DSM-IV anxiety disorders. The self-report questionnaire was included in five surveys of a longitudinal study of the Netherlands Twin Register. Genotype and phenotype data were available for 1602 twins and siblings. To estimate identity by descent , additional genotype data for 564 parents and 22 siblings were used. Linkage analyses were carried out using MERLIN-regress on the average anxiety scores across time. A linkage signal (logarithm of odds score 3.4, empirical P-value 0.07) was obtained at chromosome 14 for marker D14S65 at 105 cM (90% confidence interval, 99-115 cM bounded by markers D14S1434 and D14S985). This finding replicates a linkage finding for a broad anxiety phenotype in a clinically based sample, indicating that the region might harbor a quantitative trait locus associated with the whole spectrum of general anxiety, that is from the normal to the clinical range. Moreover, genome-wide linkage and association studies on emotionality in mice obtained significant results in a syntenic region on mouse chromosome 12. Two homolog genes lie in this region -Dlk1 (delta-like 1 homolog, Drosophila) and Rtl1 (retrotransposon-like 1). Future association studies of these genes are warranted. © 2008 Nature Publishing Group All rights reserved.

The rat genome sequencing and mapping consortium found evidence for an association between the catenin-δ2 gene (CTNND2) and anxious behaviour. We replicated these results in humans by carrying out a genetic association test in patients with panic disorder, social phobia, generalized anxiety disorder and/or agoraphobia (N = 1714) and controls (N = 4125). We further explored the association between CTNND2 and other psychiatric disorders based on publicly available genome-wide association results. A gene-based test showed that single nucleotide polymorphisms (SNPs) in CTNND2 have a significantly increased signal (P 1e(-5) ) and decreased P-values. Single nucleotide polymorphism rs1012176 showed the strongest association with any anxiety disorder (odds ratio: 0.8128, SE = 0.063, P = 0.00099), but this effect was not significant after correction for multiple testing. In available genome-wide association results from the Psychiatric Genomics Consortium we found that SNPs in CTNND2 collectively showed an increased signal for schizophrenia (P 1e(-5) ) and major depressive disorder (P 1e(-5) ), but not for bipolar disorder. These signals remained significant after correction for potential confounders. The association between CTNND2 and anxiety was not strong enough to be picked up in the current generation of human genome-wide analyses, indicating the usefulness of and need for animal genetic studies to identify candidate genes for further study in human samples.

Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N = 18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values = 1.6 x 10(-11) and 2.7 x 10(-11)), which were also in strong linkage disequilibrium (r(2) = 0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value = 3.9 x 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value = 7.1 x 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value = 2.2 x 10(-05)) and Parkinson's disease pathways (P-value = 3.6 x 10(-05)). Molecular Psychiatry (2012) 17, 1116-1129; doi: 10.1038/mp.2011.101; published online 30 August 2011

Correction to: Molecular Psychiatry (2015); advance online publication 12 January 2016; doi:10.1038/mp.2015.197 Following publication of the above article, the authors noticed that the fifteenth author’s name was presented incorrectly. The author’s name should have appeared as S Van der Auwera. The publisher regrets the error.