scholarly journals Maternal and offspring genetic risk score analyses of fetal alcohol exposure and attention‐deficit hyperactivity disorder risk in offspring

2021 ◽  
Author(s):  
Elis Haan ◽  
Hannah M. Sallis ◽  
Eivind Ystrom ◽  
Pål Rasmus Njølstad ◽  
Ole A. Andreassen ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Risk Score ◽  
Attention Deficit ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Alcohol Exposure ◽  
Fetal Alcohol Exposure ◽  
Fetal Alcohol ◽  
Hyperactivity Disorder ◽  
Disorder Risk

scholarly journals Maternal and offspring genetic risk score (GRS) analyses of fetal alcohol exposure and ADHD risk in offspring

2021 ◽  
Author(s):  
Elis Haan ◽  
Hannah M Sallis ◽  
Eivind Ystrom ◽  
Pal Rasmus Njolstad ◽  
Ole A. Andreassen ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Causal Effect ◽  
Genetic Risk Score ◽  
Alcohol Exposure ◽  
Risk Scores ◽  
Genotype Data ◽  
Fetal Alcohol Exposure ◽  
Fetal Alcohol ◽  
Maternal Genotype ◽  
Drinking Status

Background: Studies investigating the effects of prenatal alcohol exposure on childhood ADHD symptoms using conventional observational designs have reported inconsistent findings, which may be affected by unmeasured confounding and maternal and fetal ability to metabolise alcohol. We used genetic variants from alcohol metabolising genes (alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)) as proxies for fetal alcohol exposure to investigate their association with offspring ADHD risk around age 7-8. Methods: We used data from three longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC), Generation R study (GenR) and the Norwegian Mother, Father and Child Cohort study (MoBa). Genetic risk scores (GRS) for alcohol use and metabolism using 36 single nucleotide polymorphisms (SNPs) from ADH/ALDH genes were calculated for mothers (N_ALSPAC=8,196; N_MOBA=13,614), fathers (N_MOBA=13,935) and offspring (N_ALSPAC=8,237; N_MOBA=14,112; N_GENR=2,661). Associations between maternal GRS and offspring ADHD risk were tested in the full sample to avoid collider bias. Offspring GRS analyses were stratified by maternal drinking status. Results: The pooled estimate in maternal GRS analyses adjusted for offspring GRS in ALSPAC and MoBa was OR=0.99, 95%CI 0.97-1.02. The pooled estimate in offspring GRS analyses stratified by maternal drinking status across the cohorts was: OR_DRINKING=0.98, 95%CI 0.94-1.02; OR_NO DRINKING=0.99, 95%CI 0.97-1.02. These findings remained similar after accounting for maternal genotype data in ALSPAC and maternal and paternal genotype data in MoBa. Conclusions: We did not find evidence for a causal effect of fetal alcohol exposure on ADHD risk in offspring. The results may be affected by low power and outcome assessment.

scholarly journals Polygenic risk score, psychosocial environment and the risk of attention-deficit/hyperactivity disorder

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Søren D. Østergaard ◽  
Betina B. Trabjerg ◽  
Thomas D. Als ◽  
Clara Albiñana Climent ◽  
Florian Privé ◽  
...  
Keyword(s):  
Risk Factors ◽  
Attention Deficit Hyperactivity Disorder ◽  
Risk Score ◽  
Attention Deficit ◽  
Polygenic Risk Score ◽  
Environment Impact ◽  
Psychosocial Environment ◽  
Polygenic Risk ◽  
Hyperactivity Disorder ◽  
Main Effects

Abstract The objective of the present study was to investigate whether the polygenic liability for attention-deficit/hyperactivity disorder (ADHD) and the psychosocial environment impact the risk of ADHD in interaction or independently of each other. We conducted a register- and biobank-based cohort study of 13,725 individuals with ADHD and 20,147 randomly drawn population-based controls. These 33,872 cohort members were genotyped on the Infinium PsychChip v1.0 array (Illumina). Subsequently, we calculated the polygenic risk score (PRS) for ADHD and extracted register data regarding the following risk factors pertaining to the psychosocial environment for each cohort member at the time of birth: maternal/paternal history of mental disorders, maternal/paternal education, maternal/paternal work status, and maternal/paternal income. We used logistic regression analyses to assess the main effects of the PRS for ADHD and the psychosocial environment on the risk of ADHD. Subsequently, we evaluated whether the effect of the PRS and the psychosocial environment act independently or in interaction upon the risk of ADHD. We found that ADHD was strongly associated with the PRS (odds ratio: 6.03, 95%CI: 4.74–7.70 for highest vs. lowest 2% liability). All risk factors pertaining to the psychosocial environment were associated with an increased risk of ADHD. These associations were only slightly attenuated after mutual adjustments. We found no statistically significant interaction between the polygenic liability and the psychosocial environment upon the risk of ADHD. In conclusion, we found main effects of both polygenic liability and risk factors pertaining to the psychosocial environment on the risk of ADHD—in the expected direction.

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