Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesOver the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23.This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.National Institutes of Mental Health (NIMH, USA) ACE Network Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks (USA) The Autism Genome Project (AGP) from Autism Speaks (USA) Canadian Institutes of Health Research (CIHR), Genome Canada Health Research Board (Ireland) Hilibrand Foundation (USA) Medical Research Council (UK) National Institutes of Health (USA) Ontario Genomics Institute University of Toronto McLaughlin Centre Simons Foundation Johns Hopkins Autism Consortium of Boston NLM Family foundation National Institute of Health grants National Health Medical Research Council Scottish Rite Spunk Fund, Inc. Rebecca and Solomon Baker Fund APEX Foundation National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) endowment fund of the Nancy Pritzker Laboratory (Stanford) Autism Society of America Janet M. Grace Pervasive Developmental Disorders Fund The Lundbeck Foundation universities and university hospitals of Aarhus and Copenhagen Stanley Foundation Centers for Disease Control and Prevention (CDC) Netherlands Scientific Organization Dutch Brain Foundation VU University Amsterdam Trinity Centre for High Performance Computing through Science Foundation Ireland Autism Genome Project (AGP) from Autism Speak

Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders

Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways

Supplementary Material for: Intonation Adapts to Lexical Tone: The Case of Kammu

In this paper, we investigate how lexical tones interact with intonation, using data from the Austroasiatic language Kammu, one of few languages with two dialects whose only major phonological difference is the presence or absence of lexical tones. Northern (and Western) Kammu have developed tones in connection with the merger of voiceless and voiced initial consonants, while the non-tonal Eastern dialect kept the segmental opposition with no tones. We found the following prosodic hierarchy: (1) lexical tones, (2) phrase-final boundary tone, (3) focus marking. The results strongly suggest that the intonational systems of the two Kammu dialects are basically identical, and that the main differences between the dialects are adaptations of intonation patterns to the lexical tones when the identities of the tones are jeopardized

Digital Rights and Jurisdiction: The European Approach to Online Defamation and IPRs Infringements

The new media and communication technologies have significantly increased the number of online cross-border disputes involving the security and protection of personal identity as well as of intellectual property creations. The persistent lack of a uniform private international law approach on the matter deter- mines a substantial gap in Internet governance, which results in the application of domestic rules or, where existing, of regional ones. This legal scenario is conducive to conflicts of jurisdiction and, ultimately, to legal uncertainty and instances of forum shopping. The Chapter focuses on the allocation of adjudicative jurisdiction at European level by examining the current EU approach to cross-border online disputes resolution involving the main types of infringements of digital rights (notably, personality rights and IPRs). The absence of EU rules on jurisdiction concern- ing online tort disputes has encouraged the elaboration of a prolific and controversial case law of the CJEU over the interpretation of Article 7(2) of Brussels I-bis Regulation (i.e. eDate, BOÜ/Ilsjan, Wintergeister, Pinckney and Hejduk rulings). The Chapter provides a thorough and critical insight over the characteristics and trends of this development and comes to propose a brand-new “less is more” normative approach, aimed at reducing the range of eligible fora in light of a well-balanced system of assessment of the competing interests involved

Sound symbolism : The role of word sound in meaning

The question whether there is a natural connection between sound and meaning or if they are related only by convention has been debated since antiquity. In linguistics, it is usually taken for granted that 'the linguistic sign is arbitrary,' and exceptions like onomatopoeia have been regarded as marginal phenomena. However, it is becoming more and more clear that motivated relations between sound and meaning are more common and important than has been thought. There is now a large and rapidly growing literature on subjects as ideophones (or expressives), words that describe how a speaker perceives a situation with the senses, and phonaesthemes, units like English gl-, which occur in many words that share a meaning component (in this case 'light': gleam, glitter, etc.). Furthermore, psychological experiments have shown that sound symbolism in one language can be understood by speakers of other languages, suggesting that some kinds of sound symbolism are universal. For further resources related to this article, please visit the WIREs website