We present the results of a GWAS of food liking conducted on 161,625 participants from the UK-Biobank. Liking was assessed over 139 specific foods using a 9-point scale. Genetic correlations coupled ...with structural equation modelling identified a multi-level hierarchical map of food-liking with three main dimensions: "Highly-palatable", "Acquired" and "Low-caloric". The Highly-palatable dimension is genetically uncorrelated from the other two, suggesting that independent processes underlie liking high reward foods. This is confirmed by genetic correlations with MRI brain traits which show with distinct associations. Comparison with the corresponding food consumption traits shows a high genetic correlation, while liking exhibits twice the heritability. GWAS analysis identified 1,401 significant food-liking associations which showed substantial agreement in the direction of effects with 11 independent cohorts. In conclusion, we created a comprehensive map of the genetic determinants and associated neurophysiological factors of food-liking.
Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial ...consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.
It remains a challenge to determine whether children resemble their parents due to nature, nurture, or a mixture of both. Here we used a design that exploits the distinction between transmitted and ...non-transmitted alleles in genetic transmission from parent to offspring. Two separate polygenic scores (PGS) were calculated on the basis of the transmitted and non-transmitted alleles. The effect of the non-transmitted PGS is necessarily mediated by parental phenotypes, insofar as they contribute to the rearing environment of the offspring (genetic nurturing). We calculated transmitted and non-transmitted PGSs associated with adult educational attainment (EA) and PGSs associated with childhood ADHD in a general population sample of trios, i.e. child or adult offspring and their parents (N = 1120–2518). We tested if the EA and ADHD (non-)transmitted PGSs were associated with childhood academic achievement and ADHD in offspring. Based on the earlier findings for shared environment, we hypothesized to find genetic nurturing for academic achievement, but not for ADHD. In adults, both transmitted (R
2
= 7.6%) and non-transmitted (R
2
= 1.7%) EA PGSs were associated with offspring EA, evidencing genetic nurturing. In children around age 12, academic achievement was associated with the transmitted EA PGSs (R
2
= 5.7%), but we found no support for genetic nurturing (R
2
~ 0.1%). The ADHD PGSs were not significantly associated with academic achievement (R
2
~ 0.6%). ADHD symptoms in children were only associated with transmitted EA PGSs and ADHD PGSs (R
2
= 1–2%). Based on these results, we conclude that the associations between parent characteristics and offspring outcomes in childhood are mainly to be attributable to the effects of genes that are shared by parents and children.
We introduce two novel methods for multivariate genome-wide-association meta-analysis (GWAMA) of related traits that correct for sample overlap. A broad range of simulation scenarios supports the ...added value of our multivariate methods relative to univariate GWAMA. We applied the novel methods to life satisfaction, positive affect, neuroticism, and depressive symptoms, collectively referred to as the well-being spectrum (N
= 2,370,390), and found 304 significant independent signals. Our multivariate approaches resulted in a 26% increase in the number of independent signals relative to the four univariate GWAMAs and in an ~57% increase in the predictive power of polygenic risk scores. Supporting transcriptome- and methylome-wide analyses (TWAS and MWAS, respectively) uncovered an additional 17 and 75 independent loci, respectively. Bioinformatic analyses, based on gene expression in brain tissues and cells, showed that genes differentially expressed in the subiculum and GABAergic interneurons are enriched in their effect on the well-being spectrum.
We investigated whether obsessive–compulsive (OC) symptoms from a population‐based sample could be analyzed to detect genetic variants influencing obsessive–compulsive disorder (OCD). We performed a ...genome‐wide association studies (GWAS) on the obsession (rumination and impulsions) and compulsion (checking, washing, and ordering/precision) subscales of an abbreviated version of the Padua Inventory (N = 8,267 with genome‐wide genotyping and phenotyping). The compulsion subscale showed a substantial and significant positive genetic correlation with an OCD case–control GWAS (r
G = 0.61, p = .017) previously published by the Psychiatric Genomics Consortium (PGC‐OCD). The obsession subscale and the total Padua score showed no significant genetic correlations (r
G = −0.02 and r
G = 0.42, respectively). A meta‐analysis of the compulsive symptoms GWAS with the PGC‐OCD revealed no genome‐wide significant Single‐Nucleotide Polymorphisms (SNPs combined N = 17,992, indicating that the power is still low for individual SNP effects). A gene‐based association analysis, however, yielded two novel genes (WDR7 and ADCK1). The top 250 genes in the gene‐based test also showed a significant increase in enrichment for psychiatric and brain‐expressed genes. S‐Predixcan testing showed that for genes expressed in hippocampus, amygdala, and caudate nucleus significance increased in the meta‐analysis with compulsive symptoms compared to the original PGC‐OCD GWAS. Thus, the inclusion of dimensional symptom data in genome‐wide association on clinical case–control GWAS of OCD may be useful to find genes for OCD if the data are based on quantitative indices of compulsive behavior. SNP‐level power increases were limited, but aggregate, gene‐level analyses showed increased enrichment for brain‐expressed genes related to psychiatric disorders, and increased association with gene expression in brain tissues with known emotional, reward processing, memory, and fear‐formation functions.
Aims
To estimate associations between smoking initiation, smoking persistence and smoking heaviness and caffeine consumption in two population‐based samples from the Netherlands and the United ...Kingdom.
Design
Observational study employing data on self‐reported smoking behaviour and caffeine consumption.
Setting
Adults from the general population in the Netherlands and the United Kingdom.
Participants
Participants from the Netherlands Twin Register NTR: n = 21 939, mean age 40.8, standard deviation (SD) = 16.9, 62.6% female and the Avon Longitudinal Study of Parents and Children (ALSPAC: n = 9086, mean age 33.2, SD = 4.7, 100% female).
Measurements
Smoking initiation (ever versus never smoking), smoking persistence (current versus former smoking), smoking heaviness (number of cigarettes smoked) and caffeine consumption in mg per day through coffee, tea, cola and energy drinks.
Findings
After correction for age, gender (NTR), education and social class (ALSPAC), smoking initiation was associated with consuming on average 52.8 95% confidence interval (CI) = 45.6–60.0; NTR and 59.5 (95% CI = 51.8–67.2; ALSPAC) mg more caffeine per day. Smoking persistence was also associated with consuming more caffeine +57.9 (95% CI = 45.2–70.5) and +83.2 (95% CI = 70.2–96.3) mg, respectively. Each additional cigarette smoked per day was associated with 3.7 (95% CI = 1.9–5.5; NTR) and 8.4 (95% CI = 6.9–10.0; ALSPAC) mg higher daily caffeine consumption in current smokers. Smoking was associated positively with coffee consumption and less strongly with cola and energy drinks. For tea, associations were positive in ALSPAC and negative in NTR.
Conclusions
There appears to be a positive association between smoking and caffeine consumption in the Netherlands and the United Kingdom.
In recent years, multiple eQTL (expression quantitative trait loci) catalogs have become available that can help understand the functionality of complex trait-related single nucleotide polymorphisms ...(SNPs). In eQTL catalogs, gene expression is often strongly associated with multiple SNPs, which may reflect either one or multiple independent associations. Conditional eQTL analysis allows a distinction between dependent and independent eQTLs. We performed conditional eQTL analysis in 4,896 peripheral blood microarray gene expression samples. Our analysis showed that 35% of genes with a cis eQTL have at least two independent cis eQTLs; for several genes up to 13 independent cis eQTLs were identified. Also, 12% (671) of the independent cis eQTLs identified in conditional analyses were not significant in unconditional analyses. The number of GWAS catalog SNPs identified as eQTL in the conditional analyses increases with 24% as compared to unconditional analyses. We provide an online conditional cis eQTL mapping catalog for whole blood (https://eqtl.onderzoek.io/), which can be used to lookup eQTLs more accurately than in standard unconditional whole blood eQTL databases.
Studies considering the causal role of body mass index (BMI) for the predisposition of major depressive disorder (MDD) based on a Mendelian Randomization (MR) approach have shown contradictory ...results. These inconsistent findings may be attributable to the heterogeneity of MDD; in fact, several studies have documented associations between BMI and mainly the atypical subtype of MDD. Using a MR approach, we investigated the potential causal role of obesity in both the atypical subtype and its five specific symptoms assessed according to the Statistical Manual of Mental Disorders (DSM), in two large European cohorts, CoLaus|PsyCoLaus (n = 3350, 1461 cases and 1889 controls) and NESDA|NTR (n = 4139, 1182 cases and 2957 controls). We first tested general obesity measured by BMI and then the body fat distribution measured by waist-to-hip ratio (WHR). Results suggested that BMI is potentially causally related to the symptom increase in appetite, for which inverse variance weighted, simple median and weighted median MR regression estimated slopes were 0.68 (SE = 0.23, p = 0.004), 0.77 (SE = 0.37, p = 0.036), and 1.11 (SE = 0.39, p = 0.004). No causal effect of BMI or WHR was found on the risk of the atypical subtype or for any of the other atypical symptoms. Our findings show that higher obesity is likely causal for the specific symptom of increase in appetite in depressed participants and reiterate the need to study depression at the granular level of its symptoms to further elucidate potential causal relationships and gain additional insight into its biological underpinnings.
Clinically, attention-deficit/hyperactivity disorder (ADHD) is characterized by hyperactivity, impulsivity, and inattention and is among the most common childhood disorders. These same traits that ...define ADHD are variable in the general population, and the clinical diagnosis may represent the extreme end of a continuous distribution of inattentive and hyperactive behaviors. This hypothesis can be tested by assessing the predictive value of polygenic risk scores derived from a discovery sample of ADHD patients in a target sample from the general population with continuous scores of inattention and hyperactivity. In addition, the genetic overlap between ADHD and continuous ADHD scores can be tested across rater and age.
The Psychiatric Genomics Consortium has performed the largest genome-wide analysis (GWA) study of ADHD so far, including 5,621 clinical patients and 13,589 controls. The effects sizes of single nucleotide polymorphisms (SNPs) estimated in this meta-analysis were used to obtain individual polygenic risk scores in an independent population-based cohort of 2,437 children from the Netherlands Twin Register. The variance explained in Attention Problems (AP) scale scores by the polygenic risk scores was estimated by linear mixed modeling.
The ADHD polygenic risk scores significantly predicted both parent and teacher ratings of AP in preschool- and school-aged children.
These results indicate genetic overlap between a diagnosis of ADHD and AP scale scores across raters and age groups and provides evidence for a dimensional model of ADHD. Future GWA studies on ADHD can likely benefit from the inclusion of population-based cohorts and the analysis of continuous scores.
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