Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use.

Cannabis is widely used worldwide, yet its links to health outcomes are not fully understood. DNA methylation can serve as a mediator to link environmental exposures to health outcomes. We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and lifetime cannabis use (ever vs. never) in a meta-analysis including 9436 participants (7795 European and 1641 African ancestry) from seven cohorts. Accounting for effects of cigarette smoking, our trans-ancestry EWAS meta-analysis revealed four CpG sites significantly associated with lifetime cannabis use at a false discovery rate of 0.05 [Formula: see text]: cg22572071 near gene ADGRF1, cg15280358 in ADAM12, cg00813162 in ACTN1, and cg01101459 near LINC01132. Additionally, our EWAS analysis in participants who never smoked cigarettes identified another epigenome-wide significant CpG site, cg14237301 annotated to APOBR. We used a leave-one-out approach to evaluate methylation scores constructed as a weighted sum of the significant CpGs. The best model can explain 3.79% of the variance in lifetime cannabis use. These findings unravel the DNA methylation changes associated with lifetime cannabis use that are independent of cigarette smoking and may serve as a starting point for further research on the mechanisms through which cannabis exposure impacts health outcomes.

The daily reciprocal associations between electroencephalography measured sleep and affect.

Self-report studies show that sleep and positive and negative affect are closely and bidirectionally linked. However, studies assessing sleep objectively yield more inconsistent results. This study assessed the reciprocal, daily relationship between sleep as measured with electroencephalography (EEG) and affect (measured in the evening) in a natural setting. We assessed sleep both on the macrolevel (i.e., rapid eye movement [REM] sleep and slow-wave sleep [SWS] duration) and on the microlevel (i.e., REM sleep fragmentation). In this study, 33 participants (i.e., healthy college students, mean [standard deviation] age 21.55 [3.73] years, 67% female) were followed for 2 weeks. Each participant wore an EEG headband for 15 nights and had polysomnography during 3 of the 15 nights providing 72 analysable nights of polysomnography and 271 analysable nights with the EEG headband. Every evening participants reported their momentary negative and positive affect. We examined the relationship between pre-sleep affect and the sleep variables, as well as the reverse relationship, with sleep variables predicting evening affect the next day. We detected that higher negative affect in the evening was related to more fragmented REM sleep. However, this result was only found with polysomnography and not with the EEG headband. No significant associations were found between affect and time spent in REM sleep and SWS. Overall, no support was found for the reciprocal association between negative and positive affect and EEG measured sleep. Only limited support was found for an association in one direction (i.e., evening negative affect was associated with more REM sleep fragmentation at night).

Heritability of adult picky eating in the Netherlands.

Adult picky eating (APE), the rejection of familiar and unfamiliar foods leading to a diet with limited variety, is an understudied phenomenon which can have both physical and psychological negative consequences. The aetiology of individual differences in APE is understudied, although there is reason to believe that it is partly heritable. Therefore, we aimed to estimate the heritability of APE with data from the Netherlands Twin Register (n = 8016) with classical genetic structural equation modelling. In order to use these data, we firstly investigated whether a Food Preference Questionnaire (FPQ) could measure APE with a pre-registered prestudy. Adult participants (n = 414) filled in online questionnaires, including a FPQ and measures related to APE. Spearman's rho correlation quantified the relationship between different elements of the Dutch FPQ and different scores on measures of APE. Results of the prestudy showed that the mean liking score on the FPQ could be used to measure APE (ρ > .50). This measure was then used in the main study to estimate the heritability of APE. Results showed that broad-sense heritability for APE is 49 % (additive genetic effects 14 % (95 % CI [00, 38]) + dominance genetic effects 35 % (95 % CI [11, 52]), while the remaining variance is explained by unique environmental factors. Future studies may focus on uncovering the specific genetic and unique environmental factors that play a role in APE.

Childhood obesity and adolescent follow-up depressive symptoms: exploring a moderated mediation model of body esteem and gender.

Obesity is a well-recognized risk factor for adolescent depressive symptoms, but mediating mechanisms of this association have scarcely been studied. This study is unique in examining an indirect pathway of this link via body esteem (BE) prospectively from childhood (8-12 years) to adolescence (13-18 years). In addition, potential gender moderation was examined. This study utilized data from a case-control study comparing 100 children with and without obesity matched on important confounders (age, gender, and socioeconomic status). Our findings provide support for the mediating role of BE in the link between childhood weight status and adolescent depressive symptoms at a 5-year follow-up. This mediation effect did not differ between boys and girls. The findings suggest the relevance of specifically targeting children's BE in preventive intervention programs among children with obesity to prevent future mental health problems.

Is the Association Between Alcohol Consumption and Mental Well-Being in University Students Linear, Curvilinear or Absent?

Background: Both alcohol consumption and mental well-being problems have been found to be prevalent in higher educated students and often have severe consequences. However, previous findings of the association between these constructs are mixed, possibly because often linear models are fitted, while some theories suggest a curvilinear association between the two concepts. Objectives: To clarify previously mixed findings, the current study compared curvilinear and linear models for the relationship between alcohol consumption and mental well-being in university students. Because of potential gender differences in this relationship, these models were explored for females and males separately. Data from the first cross-sectional online survey wave of the Healthy Student Life project including 2,631 female and 998 male students was used. The Alcohol Use Disorders Identification Test-consumption was used to measure alcohol consumption. Mental well-being was assessed by six sub-concepts (i.e., depressive symptoms, anxiety, stress, life satisfaction, happiness, and self-rated mental health). Results: For females both linear (for anxiety, life satisfaction, and self-rated mental health) and curvilinear (for depression, stress, and happiness) associations were found, while for males no support for either curvilinear or linear models was found. Conclusions: Results should be interpreted with caution due to the small effect sizes in the relationships for females but may suggest that testing the curvilinear association between alcohol consumption and mental well-being is an important future endeavor.

Using Instrumental Variables to Measure Causation over Time in Cross-Lagged Panel Models.

Cross-lagged panel models (CLPMs) are commonly used to estimate causal influences between two variables with repeated assessments. The lagged effects in a CLPM depend on the time interval between assessments, eventually becoming undetectable at longer intervals. To address this limitation, we incorporate instrumental variables (IVs) into the CLPM with two study waves and two variables. Doing so enables estimation of both the lagged (i.e., "distal") effects and the bidirectional cross-sectional (i.e., "proximal") effects at each wave. The distal effects reflect Granger-causal influences across time, which decay with increasing time intervals. The proximal effects capture causal influences that accrue over time and can help infer causality when the distal effects become undetectable at longer intervals. Significant proximal effects, with a negligible distal effect, would imply that the time interval is too long to estimate a lagged effect at that time interval using the standard CLPM. Through simulations and an empirical application, we demonstrate the impact of time intervals on causal inference in the CLPM and present modeling strategies to detect causal influences regardless of the time interval in a study. Furthermore, to motivate empirical applications of the proposed model, we highlight the utility and limitations of using genetic variables as IVs in large-scale panel studies.

Interplay between genetic risk and the parent environment in adolescence and substance use in young adulthood: A TRAILS study.

Many adolescents start using tobacco, alcohol, and cannabis. Genetic vulnerability, parent characteristics in young adolescence, and interaction (GxE) and correlation (rGE) between these factors could contribute to the development of substance use. Using prospective data from the TRacking Adolescent Individuals' Lives Survey (TRAILS; N = 1,645), we model latent parent characteristics in young adolescence to predict young adult substance use. Polygenic scores (PGS) are created based on genome-wide association studies (GWAS) for smoking, alcohol use, and cannabis use. Using structural equation modeling we model the direct, GxE, and rGE effects of parent factors and PGS on young adult smoking, alcohol use, and cannabis initiation. The PGS, parental involvement, parental substance use, and parent-child relationship quality predicted smoking. There was GxE such that the PGS amplified the effect of parental substance use on smoking. There was rGE between all parent factors and the smoking PGS. Alcohol use was not predicted by genetic or parent factors, nor by interplay. Cannabis initiation was predicted by the PGS and parental substance use, but there was no GxE or rGE. Genetic risk and parent factors are important predictors of substance use and show GxE and rGE in smoking. These findings can act as a starting point for identifying people at risk.

A longitudinal study on changes in food parenting practices during COVID-19 and the role of parental well-being.

The COVID-19 pandemic may negatively influence food parenting practices, also among parents of adolescents. Parental well-being (stress and depressive symptoms) may explain these COVID-19 related changes in food parenting practices (snack structure, healthy structure, modeling, autonomy support, and coercive control). However, most previous studies performed before or during the COVID-19 pandemic have been limited by cross-sectional designs. The aim of the current study among parents of adolescent children was twofold. First, we aimed to examine prospective differences in food parenting practices comparing the situation before and during COVID-19. Second, we aimed to examine both cross-sectional and longitudinal associations between parental well-being and the dimensions of food parenting, while additionally examining whether these prospective associations were more pronounced in parents who had experienced more COVID-19 stressful life events. Parents (N = 290; 74.9% female; at baseline: Mage = 46.9; SDage = 4.3) of adolescent children (at baseline: Mage = 14.3; SDage = 0.6) completed online surveys about parental well-being and food parenting twice: One year before the COVID-19 pandemic (spring 2019) and during the COVID-19 pandemic, 1.5 years after the first measurement (autumn 2020). In general, we found consistent evidence for an average decrease in food autonomy support and an increase in coercive control during COVID-19. However, parental well-being did not seem to explain (changes in) food parenting practices during COVID-19, also not in combination with stressful life events. Our findings suggest that, regardless of parental well-being, the general COVID-19 situation had some small negative influences on autonomy support and coercive control among parents of adolescents. These findings might be explained by parents being more often confronted with unhealthy eating occasions in the COVID-19 home context, triggering these negative parental responses.

Investigating the causal nature of the relationship of subcortical brain volume with smoking and alcohol use.

BACKGROUND: Structural variation in subcortical brain regions has been linked to substance use, including the most commonly used substances nicotine and alcohol. Pre-existing differences in subcortical brain volume may affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. AIMS: We assess the causal nature of the complex relationship of subcortical brain volume with smoking and alcohol use, using bi-directional Mendelian randomisation. METHOD: Mendelian randomisation uses genetic variants predictive of a certain 'exposure' as instrumental variables to test causal effects on an 'outcome'. Because of random assortment at meiosis, genetic variants should not be associated with confounders, allowing less biased causal inference. We used summary-level data of genome-wide association studies of subcortical brain volumes (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus; n = 50 290) and smoking and alcohol use (smoking initiation, n = 848 460; cigarettes per day, n = 216 590; smoking cessation, n = 378 249; alcoholic drinks per week, n = 630 154; alcohol dependence, n = 46 568). The main analysis, inverse-variance weighted regression, was verified by a wide range of sensitivity methods. RESULTS: There was strong evidence that liability to alcohol dependence decreased amygdala and hippocampal volume, and smoking more cigarettes per day decreased hippocampal volume. From subcortical brain volumes to substance use, there was no or weak evidence for causal effects. CONCLUSIONS: Our findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and likely mental health, warranting more recognition in public health efforts.

The CADM2 Gene and Behavior: A Phenome-Wide Scan in UK-Biobank.

The cell adhesion molecule 2 (CADM2) gene has appeared among the top associations in a wide range of genome-wide association studies (GWASs). This study aims to: (1) examine how widespread the role of CADM2 is in behavioural traits, and (2) investigate trait-specific effects on CADM2 expression levels across tissues. We conducted a phenome-wide association study in UK Biobank (N = 12,211-453,349) on 242 psycho-behavioral traits, both at the SNP and the gene-level. For comparison, we repeated the analyses for other large (and high LD) genes. We found significant associations between CADM2 and 50 traits (including cognitive, risk taking, and dietary traits), many more than for the comparison genes. We show that many trait associations are reduced when taking geographical stratification into account. S-Predixcan revealed that CADM2 expression in brain tissues was significantly associated with many traits; highly significant effects were also observed for lung, mammary, and adipose tissues. In conclusion, this study shows that the role of CADM2 extends to a wide range of psycho-behavioral traits, suggesting these traits may share a common biological denominator.

Genetic Risk for Smoking: Disentangling Interplay Between Genes and Socioeconomic Status.

This study aims to disentangle the contribution of genetic liability, educational attainment (EA), and their overlap and interaction in lifetime smoking. We conducted genome-wide association studies (GWASs) in UK Biobank (N = 394,718) to (i) capture variants for lifetime smoking, (ii) variants for EA, and (iii) variants that contribute to lifetime smoking independently from EA ('smoking-without-EA'). Based on the GWASs, three polygenic scores (PGSs) were created for individuals from the Netherlands Twin Register (NTR, N = 17,805) and the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2, N = 3090). We tested gene-environment (G × E) interactions between each PGS, neighborhood socioeconomic status (SES) and EA on lifetime smoking. To assess if the PGS effects were specific to smoking or had broader implications, we repeated the analyses with measures of mental health. After subtracting EA effects from the smoking GWAS, the SNP-based heritability decreased from 9.2 to 7.2%. The genetic correlation between smoking and SES characteristics was reduced, whereas overlap with smoking traits was less affected by subtracting EA. The PGSs for smoking, EA, and smoking-without-EA all predicted smoking. For mental health, only the PGS for EA was a reliable predictor. There were suggestions for G × E for some relationships, but there were no clear patterns per PGS type. This study showed that the genetic architecture of smoking has an EA component in addition to other, possibly more direct components. PGSs based on EA and smoking-without-EA had distinct predictive profiles. This study shows how disentangling different models of genetic liability and interplay can contribute to our understanding of the etiology of smoking.

Examining food intake similarities in adolescent best friend dyads using longitudinal Actor-Partner Interdependence Models.

Little is known about how adolescent best friends may affect each other's food intake. This study explored whether friendship selection and socialization mechanisms explained potential food intake similarities in adolescent reciprocated best friend dyads. We also tested whether socialization processes were moderated by dyad member's relative zBMI. Members of 145 same-gender best friendship dyads (56% female; Mage = 12.79; SDage = 0.61) reported on their intake of food obtained from home and from outside the home at the beginning and the end of the school year through food frequency questionnaires. Longitudinal Actor-Partner Interdependence Models results showed no indication of selection or socialization, and very limited evidence for the moderation of socialization processes by relative zBMI. These findings indicate that focusing on adolescent reciprocated best friends in dietary interventions may not be valuable.

Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality.

Attention-deficit/hyperactivity disorder (ADHD) is a severely impairing neurodevelopmental disorder with a prevalence of 5% in children and adolescents and of 2.5% in adults. Comorbid conditions in ADHD play a key role in symptom progression, disorder course and outcome. ADHD is associated with a significantly increased risk for substance use, abuse and dependence. ADHD and cannabis use are partly determined by genetic factors; the heritability of ADHD is estimated at 70-80% and of cannabis use initiation at 40-48%. In this study, we used summary statistics from the largest available meta-analyses of genome-wide association studies (GWAS) of ADHD (n = 53,293) and lifetime cannabis use (n = 32,330) to gain insights into the genetic overlap and causal relationship of these two traits. We estimated their genetic correlation to be r2 = 0.29 (P = 1.63 × 10-5) and identified four new genome-wide significant loci in a cross-trait analysis: two in a single variant association analysis (rs145108385, P = 3.30 × 10-8 and rs4259397, P = 4.52 × 10-8) and two in a gene-based association analysis (WDPCP, P = 9.67 × 10-7 and ZNF251, P = 1.62 × 10-6). Using a two-sample Mendelian randomization approach we found support that ADHD is causal for lifetime cannabis use, with an odds ratio of 7.9 for cannabis use in individuals with ADHD in comparison to individuals without ADHD (95% CI (3.72, 15.51), P = 5.88 × 10-5). These results substantiate the temporal relationship between ADHD and future cannabis use and reinforce the need to consider substance misuse in the context of ADHD in clinical interventions.

Associations between the CADM2 gene, substance use, risky sexual behavior, and self-control: A phenome-wide association study.

Risky behaviors, such as substance use and unprotected sex, are associated with various physical and mental health problems. Recent genome-wide association studies indicated that variation in the cell adhesion molecule 2 (CADM2) gene plays a role in risky behaviors and self-control. In this phenome-wide scan for risky behavior, it was tested if underlying common vulnerability could be (partly) explained by pleiotropic effects of this gene and how large the effects were. Single nucleotide polymorphism (SNP)-level and gene-level association tests within four samples (25 and Up, Spit for Science, Netherlands Twin Register, and UK Biobank and meta-analyses over all samples (combined sample of 362,018 participants) were conducted to test associations between CADM2, substance- and sex-related risk behaviors, and various measures related to self-control. We found significant associations between the CADM2 gene, various risky behaviors, and different measures of self-control. The largest effect sizes were found for cannabis use, sensation seeking, and disinhibition. Effect sizes ranged from 0.01% to 0.26% for single top SNPs and from 0.07% to 3.02% for independent top SNPs together, with sufficient power observed only in the larger samples and meta-analyses. In the largest cohort, we found indications that risk-taking proneness mediated the association between CADM2 and latent factors for lifetime smoking and regular alcohol use. This study extends earlier findings that CADM2 plays a role in risky behaviors and self-control. It also provides insight into gene-level effect sizes and demonstrates the feasibility of testing mediation. These findings present a good starting point for investigating biological etiological pathways underlying risky behaviors.

Food parenting practices and children's weight outcomes: A systematic review of prospective studies.

This systematic review is the first to provide an overview of the prospective links between food parenting practices and children's weight outcomes. Three databases were searched. All titles, abstracts and full-texts were double screened by two independent reviewers. Peer-reviewed journal articles published after 1990 assessing the prospective association between food parenting practices and weight outcomes of children aged 2-18 years were eligible. A total of 38 eligible studies were identified, focusing on 12 separate food parenting practices. Restriction, pressure to eat, and monitoring were generally not associated with children's weight over time, but higher quality studies suggest that pressure to eat was associated with lower weight outcomes over time. Most studies on food availability and accessibility found null-findings as well. Instrumental-but not emotional-feeding was associated with higher weight over time, but higher quality studies are needed to confirm this link. Results involving the link between frequency of mealtime and child weight were mixed. Autonomy supporting and other structure-related food parenting practices were understudied. In conclusion, food parenting practices receiving the most attention within prospective studies (i.e., restriction, pressure to eat, monitoring) were generally not associated with children's weight outcomes over time. Future high quality studies should focus more on other food parenting practices, further unravel bidirectional links between food parenting and children's eating behaviors and weight outcomes, and examine the mediating role of dietary intake.

Investigating genetic correlation and causality between nicotine dependence and ADHD in a broader psychiatric context.

People with attention-deficit/hyperactivity disorder (ADHD) or other psychiatric disorders show high rates of nicotine dependence (ND). This comorbidity might be (partly) explained by shared genetic factors. Genetic correlations between ND and ADHD (or other psychiatric disorders) have not yet been estimated. A significant genetic correlation might indicate genetic overlap, but could also reflect a causal relationship. In the present study we investigated the genetic correlation (with LD score regression analyses) between ND and ADHD, as well as between ND and other major psychiatric conditions (major depressive disorder, schizophrenia, anxiety, bipolar disorder, autism spectrum, anorexia nervosa, and antisocial behavior) based on the summary statistics of large Genome Wide Association studies. We explored the causal nature of the relationship between ND and ADHD using two-sample Mendelian randomization. We found a high genetic correlation between ND and ADHD (rg  = .53, p = 1.85 × 10-13 ), and to a lesser extent also between ND-major depressive disorder (rg  = .42, p = 3.6 × 10-11 ) and ND-schizophrenia (rg  = .18, p = 1.1 × 10-3 ). We did not find evidence for a causal relationship from liability for ADHD to ND (which could be due to a lack of power). The strong genetic correlations might reflect different phenotypic manifestations of (partly) shared underlying genetic vulnerabilities. Combined with the lack of evidence for a causal relationship from liability for ADHD to ND, these findings stress the importance to further investigate the underlying genetic vulnerability explaining co-morbidity in psychiatric disorders.

Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes.

INTRODUCTION: FTND (FagerstrÓ§m test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported. METHODS: Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts. RESULTS: We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND. CONCLUSIONS: Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND. IMPLICATIONS: Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways.

The generalizability of Older Adult Self-Report (OASR) syndromes of psychopathology across 20 societies.

OBJECTIVES: As the world population ages, psychiatrists will increasingly need instruments for measuring constructs of psychopathology that are generalizable to diverse elders. The study tested whether syndromes of co-occurring problems derived from self-ratings of psychopathology by US elders would fit self-ratings by elders in 19 other societies. METHODS/DESIGN: The Older Adult Self-Report (OASR) was completed by 12 826 adults who were 60 to 102 years old in 19 societies from North and South America, Asia, and Eastern, Northern, Southern, and Western Europe, plus the United States. Individual and multigroup confirmatory factor analyses (CFAs) tested the fit of the seven-syndrome OASR model, consisting of the Anxious/Depressed, Worries, Somatic Complaints, Functional Impairment, Memory/Cognition Problems, Thought Problems, and Irritable/Disinhibited syndromes. RESULTS: In individual CFAs, the primary model fit index showed good fit for all societies, while the secondary model fit indices showed acceptable to good fit. The items loaded strongly on their respective factors, with a median item loading of .63 across 20 societies, and 98.7% of the loadings were statistically significant. In multigroup CFAs, 98% of items demonstrated approximate or full metric invariance. Fifteen percent of items demonstrated approximate or full scalar invariance, and another 59% demonstrated scalar invariance across more than half of societies. CONCLUSIONS: The findings supported the generalizability of OASR syndromes across societies. The seven syndromes offer empirically based clinical constructs that are relevant for elders of different backgrounds. They can be used to assess diverse elders and as a taxonomic framework to facilitate communication, services, research, and training in geriatric psychiatry.

Causes of Variation in Food Preference in the Netherlands.

Our current society is characterized by an increased availability of industrially processed foods with high salt, fat and sugar content. How is it that some people prefer these unhealthy foods while others prefer more healthy foods? It is suggested that both genetic and environmental factors play a role. The aim of this study was to (1) identify food preference clusters in the largest twin-family study into food preference to date and (2) determine the relative contribution of genetic and environmental factors to individual differences in food preference in the Netherlands. Principal component analysis was performed to identify the preference clusters by using data on food liking/disliking from 16,541 adult multiples and their family members. To estimate the heritability of food preference, the data of 7833 twins were used in structural equation models. We identified seven food preference clusters (Meat, Fish, Fruits, Vegetables, Savory snacks, Sweet snacks and Spices) and one cluster with Drinks. Broad-sense heritability (additive [A] + dominant [D] genetic factors) for these clusters varied between .36 and .60. Dominant genetic effects were found for the clusters Fruit, Fish (males only) and Spices. Quantitative sex differences were found for Meat, Fish and Savory snacks and Drinks. To conclude, our study convincingly showed that genetic factors play a significant role in food preference. A next important step is to identify these genes because genetic vulnerability for food preference is expected to be linked to actual food consumption and different diet-related disorders.

Identification of Common Genetic Variants Influencing Spontaneous Dizygotic Twinning and Female Fertility.

Spontaneous dizygotic (DZ) twinning occurs in 1%-4% of women, with familial clustering and unknown physiological pathways and genetic origin. DZ twinning might index increased fertility and has distinct health implications for mother and child. We performed a GWAS in 1,980 mothers of spontaneous DZ twins and 12,953 control subjects. Findings were replicated in a large Icelandic cohort and tested for association across a broad range of fertility traits in women. Two SNPs were identified (rs11031006 near FSHB, p = 1.54 × 10(-9), and rs17293443 in SMAD3, p = 1.57 × 10(-8)) and replicated (p = 3 × 10(-3) and p = 1.44 × 10(-4), respectively). Based on ∼90,000 births in Iceland, the risk of a mother delivering twins increased by 18% for each copy of allele rs11031006-G and 9% for rs17293443-C. A higher polygenic risk score (PRS) for DZ twinning, calculated based on the results of the DZ twinning GWAS, was significantly associated with DZ twinning in Iceland (p = 0.001). A higher PRS was also associated with having children (p = 0.01), greater lifetime parity (p = 0.03), and earlier age at first child (p = 0.02). Allele rs11031006-G was associated with higher serum FSH levels, earlier age at menarche, earlier age at first child, higher lifetime parity, lower PCOS risk, and earlier age at menopause. Conversely, rs17293443-C was associated with later age at last child. We identified robust genetic risk variants for DZ twinning: one near FSHB and a second within SMAD3, the product of which plays an important role in gonadal responsiveness to FSH. These loci contribute to crucial aspects of reproductive capacity and health.