How and why we should move beyond natural selection in museums to tackle teleology.

Background: Museum displays commonly use a "VIST" approach (Variation, Inheritance, Selection, and Time) to explain evolution to visitors. I contend that this framework, by focusing narrowly on natural selection, unintentionally reinforces intuitive teleological thinking and a "survival of the fittest" mentality. Exhibits that incorporate all the forces (or mechanisms) of evolution will instead challenge visitors' preconceptions and enable them to develop a deeper understanding of evolution. In particular, visitors will appreciate that evolution is not progressive, with modern humans as the "most evolved" species. Results: Explicit and implicit description of the forces of evolution is surveyed in 12 museums: 4 in Texas, 7 elsewhere in the U.S., and the Natural History Museum in London. Museum exhibits focus primarily on natural selection (explicit in 10 of 12) and often mention mutation (explicit in 7). Only the American Museum of Natural History in New York, in my sample, provides an explicit explanation of genetic drift. Conclusions: Heavy emphasis on natural selection and limited explanation of stochastic forces contributes to an impoverished view of evolution. Exhibits should more effectively convey the complexity of microevolution. Computer simulations showing the interactions of evolutionary forces can accomplish this goal.

Discovery of 42 genome-wide significant loci associated with dyslexia.

Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.

Implementation and Outcomes of a Train-the-Trainer Program at Behavioral Health Treatment Centers as a Mechanism to Maintain Organizational Capacity to Address Tobacco Use Disorder.

Despite prior successful implementation of Taking Texas Tobacco Free (TTTF), an evidence-based tobacco-free workplace program, in local mental health authorities (LMHAs), post-implementation employee attrition necessitated continuing education on tobacco-free policies and tobacco treatment practices. Here, we report on the outcomes of a train-the-trainer program which trained "champions" to deliver tobacco cessation education at their LMHAs. Three LMHAs participated in program implementation via 10 champions, iteratively trained and coached by TTTF. Measures administered evaluated four goals: (1) increase champions' self-efficacy in delivering trainings, (2) achieve program fidelity via TTTF staff evaluation of trainer effectiveness and knowledge increases among attending employees, (3) achieve stakeholder program acceptability, and (4) achieve program adoption via an increase in follow-up trainings. Champions' self-efficacy increased throughout TTTF training. TTTF staff ratings of champion-led trainings met the targeted range for trainer effectiveness; employees had a 28.71% knowledge increase over baseline post-training (p < 0.001). Employees rated champions' training delivery "very good" to "excellent", on average; both champions and employees were, on average, "satisfied" to "extremely satisfied" with the curriculum and training received. There was an increase over baseline in trainings delivered during follow-up, and trainings increased in length and topic coverage. Ultimately, the train-the-trainer program achieved the intended goals, although not all changes were statistically significant, likely at least partially attributable to small sample sizes. Overall, these results suggest that TTTF's train-the-trainer program was successful in its delivery and intention to build capacity for the provision of in-house tobacco education trainings to behavioral health employees/providers. However, further evaluation in additional settings, with more champions, et cetera, is necessary to validate these findings, ensure their replicability, link program implementation with reduced patient tobacco use rates, and assess long-term sustainability.

Evaluation of the implementation of a best practice gestational diabetes model of care in two Australian metropolitan services.

INTRODUCTION AND AIMS: Dissemination and local adaptation of best practice models of care are often poorly achieved in knowledge translation processes. Understanding and documenting the iterative cycles of improvement can elucidate barriers, enablers and benefits of the process for future adoption and service integration improvements. This project examined the process of local adaptation for a third stage translation of a gestational diabetes dietetic model of care through collaboration with two Queensland (Australia) hospitals. METHODS: Using a hub (research team)-spoke (sites) model, two Queensland Hospital and Health Service Districts were supported to assess and address evidence-practice dietetic model of care gaps in their gestational diabetes mellitus (GDM) services. Sites selected demonstrated strong GDM team cohesiveness and project commitment. The project phases were: Consultation; Baseline; Transition; Implementation; and Evaluation. RESULTS: Despite strong site buy-in and use of a previously successful model of care dissemination and adoption strategy, unexpected global, organisational, team and individual barriers prevented successful implementation of the model of care at both sites. Barriers included challenges with ethics and governance requirements for health service research, capacity to influence and engage multidisciplinary teams, staff turnover and coronavirus disease 2019's (COVID-19's) disruption to service delivery. CONCLUSION: This third iteration of the dissemination of a best practice model of nutrition care for GDM in two Queensland Hospital and Health Service Districts did not achieve successful clinical or process outcomes. However, valuable learnings and recommendations regarding future clinical and research health service redesign aligned with best practice are suggested.

A rare missense variant in the ATP2C2 gene is associated with language impairment and related measures.

At least 5% of children present unexpected difficulties in expressing and understanding spoken language. This condition is highly heritable and often co-occurs with other neurodevelopmental disorders such as dyslexia and ADHD. Through an exome sequencing analysis, we identified a rare missense variant (chr16:84405221, GRCh38.p12) in the ATP2C2 gene. ATP2C2 was implicated in language disorders by linkage and association studies, and exactly the same variant was reported previously in a different exome sequencing study for language impairment (LI). We followed up this finding by genotyping the mutation in cohorts selected for LI and comorbid disorders. We found that the variant had a higher frequency in LI cases (1.8%, N = 360) compared with cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24 046 gnomAD controls). Additionally, we observed that carriers of the rare variant identified from a general population cohort (N = 42, ALSPAC cohort) presented, as a group, lower scores on a range of reading and language-related measures compared to controls (N = 1825; minimum P = 0.002 for non-word reading). ATP2C2 encodes for an ATPase (SPCA2) that transports calcium and manganese ions into the Golgi lumen. Our functional characterization suggested that the rare variant influences the ATPase activity of SPCA2. Thus, our results further support the role of ATP2C2 locus in language-related phenotypes and pinpoint the possible effects of a specific rare variant at molecular level.

Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia.

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10-6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10-13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10-43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10-22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10-12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10-4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10-7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10-29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.

Pedigree-Based Gene Mapping Supports Previous Loci and Reveals Novel Suggestive Loci in Specific Language Impairment.

Purpose Specific language impairment (SLI) is characterized by a delay in language acquisition despite a lack of other developmental delays or hearing loss. Genetics of SLI is poorly understood. The purpose of this study is to identify SLI genetic loci through family-based linkage mapping. Method We performed genome-wide parametric linkage analysis in six families segregating with SLI. An age-appropriate standardized omnibus language measure was used to categorically define the SLI phenotype. Results A suggestive linkage region replicated a previous region of interest with the highest logarithm of odds (LOD) score of 2.40 at 14q11.2-q13.3 in Family 489. A paternal parent-of-origin effect associated with SLI and language phenotypes on a nonsynonymous single nucleotide polymorphism (SNP) in NOP9 (14q12) was reported previously. Linkage analysis identified a new SLI locus at 15q24.3-25.3 with the highest parametric LOD score of 3.06 in Family 315 under a recessive mode of inheritance. Suggestive evidence of linkage was also revealed at 4q31.23-q35.2 in Family 300, with the highest LOD score of 2.41. Genetic linkage was not identified in the other three families included in parametric linkage analysis. Conclusions These results are the first to report genome-wide suggestive linkage with a total language standard score on an age-appropriate omnibus language measure across a wide age range. Our findings confirm previous reports of a language-associated locus on chromosome 14q, report new SLI loci, and validate the pedigree-based parametric linkage analysis approach to mapping genes for SLI. Supplemental Material https://doi.org/10.23641/asha.13203218.

Human manual distal phalanges from the Middle Stone Age deposits of Klasies River Main Site, Western Cape Province, South Africa.

Two new distal manual phalanges from the Middle Stone Age deposits of Klasies River Main Site are described. One (SAM-AP 6387) likely derives from ray II or ray III, whereas the other (SAM-AP 6388) is from the thumb. Both derive from a late adolescent or fully adult individual. They were recovered by H. Deacon from the same stratigraphic unit (submember W or possibly submember R) of the Shell and Sand Member of Cave 1, which places them between 100 and 90 ka. Both are comparatively small elements, and the possibility that they came from the same hand cannot be discounted at this time. These bones add to the meager and all too fragmentary postcranial human fossil sample from the Late Pleistocene of South Africa. These two specimens provide some additional evidence pertaining to the morphological attributes of the distal phalanges of the Middle Stone Age inhabitants of South Africa. Together with the distal pollical phalanx from Die Kelders (SAM-AP 6402), they are relatively small in comparison with homologs from recent human samples as well as Late Pleistocene specimens from Eurasia. Given their small sizes, the distal pollical phalanges from Klasies and Die Kelders are not dissimilar to Holocene Khoesan homologs. As expected, the Klasies elements differ noticeably from Neandertal homologs, especially in the narrowness of their shafts and distal tuberosities.

Multivariate genome-wide association study of rapid automatised naming and rapid alternating stimulus in Hispanic American and African-American youth.

BACKGROUND: Rapid automatised naming (RAN) and rapid alternating stimulus (RAS) are reliable predictors of reading disability. The underlying biology of reading disability is poorly understood. However, the high correlation among RAN, RAS and reading could be attributable to shared genetic factors that contribute to common biological mechanisms. OBJECTIVE: To identify shared genetic factors that contribute to RAN and RAS performance using a multivariate approach. METHODS: We conducted a multivariate genome-wide association analysis of RAN Objects, RAN Letters and RAS Letters/Numbers in a sample of 1331 Hispanic American and African-American youth. Follow-up neuroimaging genetic analysis of cortical regions associated with reading ability in an independent sample and epigenetic examination of extant data predicting tissue-specific functionality in the brain were also conducted. RESULTS: Genome-wide significant effects were observed at rs1555839 (p=4.03×10-8) and replicated in an independent sample of 318 children of European ancestry. Epigenetic analysis and chromatin state models of the implicated 70 kb region of 10q23.31 support active transcription of the gene RNLS in the brain, which encodes a catecholamine metabolising protein. Chromatin contact maps of adult hippocampal tissue indicate a potential enhancer-promoter interaction regulating RNLS expression. Neuroimaging genetic analysis in an independent, multiethnic sample (n=690) showed that rs1555839 is associated with structural variation in the right inferior parietal lobule. CONCLUSION: This study provides support for a novel trait locus at chromosome 10q23.31 and proposes a potential gene-brain-behaviour relationship for targeted future functional analysis to understand underlying biological mechanisms for reading disability.

Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia.

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468). We observed a genome-wide significant effect (p < 1 × 10-8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 × 10-9), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 × 10-8). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 × 10-8) and with all the cognitive traits tested (p = 3.07 × 10-8), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p ~ [10-5-10-7]) and negatively associated with ADHD PRS (p ~ [10-8-10-17]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.

Splice-altering variant in COL11A1 as a cause of nonsyndromic hearing loss DFNA37.

PURPOSE: The aim of this study was to determine the genetic cause of autosomal dominant nonsyndromic hearing loss segregating in a multigenerational family. METHODS: Clinical examination, genome-wide linkage analysis, and exome sequencing were carried out on the family. RESULTS: Affected individuals presented with early-onset progressive mild hearing impairment with a fairly flat, gently downsloping or U-shaped audiogram configuration. Detailed clinical examination excluded any additional symptoms. Linkage analysis detected an interval on chromosome 1p21 with a logarithm of the odds (LOD) score of 8.29: designated locus DFNA37. Exome sequencing identified a novel canonical acceptor splice-site variant c.652-2A>C in the COL11A1 gene within the DFNA37 locus. Genotyping of all 48 family members confirmed segregation of this variant with the deafness phenotype in the extended family. The c.652-2A>C variant is novel, highly conserved, and confirmed in vitro to alter RNA splicing. CONCLUSION: We have identified COL11A1 as the gene responsible for deafness at the DFNA37 locus. Previously, COL11A1 was solely associated with Marshall and Stickler syndromes. This study expands its phenotypic spectrum to include nonsyndromic deafness. The implications of this discovery are valuable in the clinical diagnosis, prognosis, and treatment of patients with COL11A1 pathogenic variants.

Noncovalent Interactions between Trimethylamine N-Oxide (TMAO), Urea, and Water.

Trimethylamine N-oxide (TMAO) and urea are two important osmolytes with their main significance to the biophysical field being in how they uniquely interact with proteins. Urea is a strong protein destabilizing agent, whereas TMAO is known to counteract urea's deleterious effects. The exact mechanisms by which TMAO stabilizes and urea destabilizes folded proteins continue to be debated in the literature. Although recent evidence has suggested that urea binds directly to amino acid side chains to make protein folding less thermodynamically favored, it has also been suggested that urea acts indirectly to denature proteins by destabilizing the surrounding hydrogen bonding water networks. Here, we elucidate the molecular level mechanism of TMAO's unique ability to counteract urea's destabilizing nature by comparing Raman spectroscopic frequency shifts to the results of electronic structure calculations of microsolvated molecular clusters. Experimental and computational data suggest that the addition of TMAO into an aqueous solution of urea induces blue shifts in urea's H-N-H symmetric bending modes, which is evidence for direct interactions between the two cosolvents.

Single (sub)species then and now: An examination of the nonracial perspective of C. Loring Brace.

C. Loring Brace's writings on the concept of race have been among the most influential within anthropology. A review of the development of Brace's perspective on race shows that his philosophical approaches to fossil and modern human variation are consistent and integrated. Brace's views on race are compared with those of Ashley Montagu and Frank Livingstone, who also proposed eliminating "race" from anthropology, and with those of Stanley Garn and Alice Brues, who accepted "racial" subdivisions of humans. Carleton Coon's writings are more divergent; the aftermath of the publication of his Origin of Races highlights significant political tensions of the 1960s that intersected with scientific changes in anthropology emanating from the Evolutionary Synthesis. Recent forensic and "no race" positions are compared to explore their differences and the possibility of reconciliation, and the role of Brace and others in combating proposals of intellectual differences among human groups is discussed. While a spectrum of anthropological opinion regarding race exists, the commonalities are sufficient to allow valuable, united commentary emphasizing the complexity of modern human cultural and biological variation.

Enrichment of putatively damaging rare variants in the DYX2 locus and the reading-related genes CCDC136 and FLNC.

Eleven loci with prior evidence for association with reading and language phenotypes were sequenced in 96 unrelated subjects with significant impairment in reading performance drawn from the Colorado Learning Disability Research Center collection. Out of 148 total individual missense variants identified, the chromosome 7 genes CCDC136 and FLNC contained 19. In addition, a region corresponding to the well-known DYX2 locus for RD contained 74 missense variants. Both allele sets were filtered for a minor allele frequency ≤0.01 and high Polyphen-2 scores. To determine if observations of these alleles are occurring more frequently in our cases than expected by chance in aggregate, counts from our sample were compared to the number of observations in the European subset of the 1000 Genomes Project using Fisher's exact test. Significant P values were achieved for both CCDC136/FLNC (P = 0.0098) and the DYX2 locus (P = 0.012). Taken together, this evidence further supports the influence of these regions on reading performance. These results also support the influence of rare variants in reading disability.

Investigating the effects of copy number variants on reading and language performance.

BACKGROUND: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs). METHODS: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes). Then, we computed the correlation between measures of CNV genomic burden and the first principal component (PC) score derived from several continuous reading and language traits, both before and after adjustment for performance IQ. Finally, we screened the genome, probe-by-probe, for association with the PC scores, through two complementary analyses: we tested a binary CNV state assigned for the location of each probe (i.e., CNV+ or CNV-), and we analyzed continuous probe intensity data using FamCNV. RESULTS: No significant correlation was found between measures of CNV burden and PC scores, and no genome-wide significant associations were detected in probe-by-probe screening. Nominally significant associations were detected (p~10(-2)-10(-3)) within CNTN4 (contactin 4) and CTNNA3 (catenin alpha 3). These genes encode cell adhesion molecules with a likely role in neuronal development, and they have been previously implicated in autism and other neurodevelopmental disorders. A further, targeted assessment of candidate CNV regions revealed associations with the PC score (p~0.026-0.045) within CHRNA7 (cholinergic nicotinic receptor alpha 7), which encodes a ligand-gated ion channel and has also been implicated in neurodevelopmental conditions and language impairment. FamCNV analysis detected a region of association (p~10(-2)-10(-4)) within a frequent deletion ~6 kb downstream of ZNF737 (zinc finger protein 737, uncharacterized protein), which was also observed in the association analysis using CNV calls. CONCLUSIONS: These data suggest that CNVs do not underlie a substantial proportion of variance in reading and language skills. Analysis of additional, larger datasets is warranted to further assess the potential effects that we found and to increase the power to detect CNV effects on reading and language.

The regulatory element READ1 epistatically influences reading and language, with both deleterious and protective alleles.

BACKGROUND: Reading disability (RD) and language impairment (LI) are heritable learning disabilities that obstruct acquisition and use of written and spoken language, respectively. We previously reported that two risk haplotypes, each in strong linkage disequilibrium (LD) with an allele of READ1, a polymorphic compound short tandem repeat within intron 2 of risk gene DCDC2, are associated with RD and LI. Additionally, we showed a non-additive genetic interaction between READ1 and KIAHap, a previously reported risk haplotype in risk gene KIAA0319, and that READ1 binds the transcriptional regulator ETV6. OBJECTIVE: To examine the hypothesis that READ1 is a transcriptional regulator of KIAA0319. METHODS: We characterised associations between READ1 alleles and RD and LI in a large European cohort, and also assessed interactions between READ1 and KIAHap and their effect on performance on measures of reading, language and IQ. We also used family-based data to characterise the genetic interaction, and chromatin conformation capture (3C) to investigate the possibility of a physical interaction between READ1 and KIAHap. RESULTS AND CONCLUSIONS: READ1 and KIAHap show interdependence--READ1 risk alleles synergise with KIAHap, whereas READ1 protective alleles act epistatically to negate the effects of KIAHap. The family data suggest that these variants interact in trans genetically, while the 3C results show that a region of DCDC2 containing READ1 interacts physically with the region upstream of KIAA0319. These data support a model in which READ1 regulates KIAA0319 expression through KIAHap and in which the additive effects of READ1 and KIAHap alleles are responsible for the trans genetic interaction.

Twenty-First Century "Eugenics"?: The Enduring Legacy.

Despite pronounced changes in genetic knowledge and technology, the post-World War II philosophical stance on "eugenics" has not changed substantially. By the mid-1900s, as classical eugenics became less genetically naive and the medical profession became increasingly oriented toward disease prevention, a reformed eugenics had greater appeal. Eugenics' surviving influence on medical genetics is best seen in the field of genetic counseling, a discipline that serves prospective parents and families at risk of genetic abnormalities, and whose origins reveal close ties to population genetics. This article examines the ideal of nondirective counseling, genetic screening for disease, concerns regarding the quality of children, and the potential to select the sex and other characteristics of future offspring in order to indicate the complexity of ethical issues in modern genetic counseling. Modern "eugenics" is prevention-focused and has, importantly, eschewed outmoded and invidious "racial" distinctions, but these seminal tendencies are evident by the mid-20th century.

Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ.

Reading disability (RD) and language impairment (LI) are common neurodevelopmental disorders with moderately strong genetic components and lifelong implications. RD and LI are marked by unexpected difficulty acquiring and processing written and verbal language, respectively, despite adequate opportunity and instruction. RD and LI-and their associated deficits-are complex, multifactorial, and often comorbid. Genetic studies have repeatedly implicated the DYX2 locus, specifically the genes DCDC2 and KIAA0319, in RD, with recent studies suggesting they also influence LI, verbal language, and cognition. Here, we characterize the relationship of the DYX2 locus with RD, LI, and IQ. To accomplish this, we developed a marker panel densely covering the 1.4 Mb DYX2 locus and assessed association with reading, language, and IQ measures in subjects from the Avon Longitudinal Study of Parents and Children. We then replicated associations in three independent, disorder-selected cohorts. As expected, there were associations with known RD risk genes KIAA0319 and DCDC2. In addition, we implicated markers in or near other DYX2 genes, including TDP2, ACOT13, C6orf62, FAM65B, and CMAHP. However, the LD structure of the locus suggests that associations within TDP2, ACOT13, and C6orf62 are capturing a previously reported risk variant in KIAA0319. Our results further substantiate the candidacy of KIAA0319 and DCDC2 as major effector genes in DYX2, while proposing FAM65B and CMAHP as new DYX2 candidate genes. Association of DYX2 with multiple neurobehavioral traits suggests risk variants have functional consequences affecting multiple neurological processes. Future studies should dissect these functional, possibly interactive relationships of DYX2 candidate genes.