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Haavik, J.

Publications and source records attributed to Haavik, J..

2 recordsLinked to original sources
bioRxiv2019

The Role of Gene Encoding Variation of DRD4 in the Relationship between Inattention and Seasonal Daylight

Daylight is the strongest synchronizer of human circadian rhythms. The circadian pathway hypothesis posits that synchrony between daylight and the circadian system relates to (in)attention. The dopamine neurotransmitter system is implicated in regulating the circadian system as well as in (attention)-deficit hyperactivity disorder [ADHD]. We studied the role of functional genetic variation in the gene encoding of dopamine-receptor-D4 (DRD4) in the relationship between inattention and seasonal daylight (changes). Gene-by-environment (GxE) mega-analyses were performed across eight studies including 3757 adult participants (with and without ADHD). We tested 1) the Spring-focus hypothesis, in which attention in 7R-carriers normalizes with increasing daylight levels preceding measurement, 2) the Summer-born ADHD hypothesis, in which 7R-carriers report more inattention when born in spring/summer than in autumn/winter, 3) the Winter-born ADHD hypothesis, opposing the second hypothesis. The Spring-focus hypothesis was upheld (1386 ADHD, 760 controls; d=-0.16 between periods); 7R-carriers reported even less inattention than 7R-non-carriers after winter solstice (d=0.27 between genotype-groups). Results were diagnosis-independent. Sensitivity analyses at individual study level confirmed the circannual patterns for 7R-carriers. Incorporating geographic changes into the independent measure, we also calculated changes in sunlight levels. This approach likewise showed that inattention correlated negatively with increasing light levels in 7R-carriers (r=-.135). Results emphasize peripheral effects of dopamine and the effects of (seasonal) daylight changes on cognition.

genetics↗
bioRxiv2019

Cross-disorder GWAS meta-analysis for Attention Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Obsessive Compulsive Disorder, and Tourette Syndrome

Attention Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Obsessive-Compulsive Disorder (OCD), and Tourette Syndrome (TS) are among the most prevalent neurodevelopmental psychiatric disorders of childhood and adolescence. High comorbidity rates across these four disorders point toward a common etiological thread that could be connecting them across the repetitive behaviors-impulsivity-compulsivity continuum. Aiming to uncover the shared genetic basis across ADHD, ASD, OCD, and TS, we undertake a systematic cross-disorder meta-analysis, integrating summary statistics from all currently available genome-wide association studies (GWAS) for these disorders, as made available by the Psychiatric Genomics Consortium (PGC) and the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). We present analysis of a combined dataset of 93,294 individuals, across 6,788,510 markers and investigate associations on the single-nucleotide polymorphism (SNP), gene and pathway levels across all four disorders but also pairwise. In the ADHD-ASD-OCD-TS cross disorder GWAS meta-analysis, we uncover in total 297 genomewide significant variants from six LD (linkage disequilibrium) -independent genomic risk regions. Out of these genomewide significant association results, 199 SNPs, that map onto four genomic regions, show high posterior probability for association with at least three of the studied disorders (m-value>0.9). Gene-based GWAS meta-analysis across ADHD, ASD, OCD, and TS identified 21 genes significantly associated under Bonferroni correction. Out of those, 15 could not be identified as significantly associated based on the individual disorder GWAS dataset, indicating increased power in the cross-disorder comparisons. Cross-disorder tissue-specificity analysis implicates the Hypothalamus-Pituitary-Adrenal axis (stress response) as possibly underlying shared pathophysiology across ADHD, ASD, OCD, and TS. Our work highlights genetic variants and genes that may contribute to overlapping neurobiology across the four studied disorders and highlights the value of re-defining the framework for the study across this spectrum of highly comorbid disorders, by using transdiagnostic approaches.

genetics↗