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 Identifying individuals with high risk of Alzheimer’s disease using polygenic risk scores

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ganna Leonenko ◽  
Emily Baker ◽  
Joshua Stevenson-Hoare ◽  
Annerieke Sierksma ◽  
Mark Fiers ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Genetic Risk ◽  
Prediction Accuracy ◽  
Genetic Risk Score ◽  
Low Risk ◽  
Risk Scores ◽  
Sample Mean ◽  
Polygenic Risk ◽  
Reliable Identification

AbstractPolygenic Risk Scores (PRS) for AD offer unique possibilities for reliable identification of individuals at high and low risk of AD. However, there is little agreement in the field as to what approach should be used for genetic risk score calculations, how to model the effect of APOE, what the optimal p-value threshold (pT) for SNP selection is and how to compare scores between studies and methods. We show that the best prediction accuracy is achieved with a model with two predictors (APOE and PRS excluding APOE region) with pT<0.1 for SNP selection. Prediction accuracy in a sample across different PRS approaches is similar, but individuals’ scores and their associated ranking differ. We show that standardising PRS against the population mean, as opposed to the sample mean, makes the individuals’ scores comparable between studies. Our work highlights the best strategies for polygenic profiling when assessing individuals for AD risk.

scholarly journals Fetal Alcohol Exposure Disrupts Metabolic Signaling in Hypothalamic Proopiomelanocortin Neurons via a Circadian Mechanism in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (7) ◽  
pp. 2578-2588 ◽  
Author(s):  
Maria A. Agapito ◽  
Changqing Zhang ◽  
Sengottuvelan Murugan ◽  
Dipak K. Sarkar
Keyword(s):  
Alcohol Exposure ◽  
Male Mice ◽  
Fetal Alcohol Exposure ◽  
Fetal Alcohol ◽  
Metabolic Signaling

Prevalence of heavy fetal alcohol exposure by analysis of meconium fatty acid ethyl esters; A nat ionwide canadian study

2018 ◽  
Vol 80 ◽  
pp. 142
Author(s):  
Kaithlyn Delano ◽  
Gideon Koren ◽  
Martin Zack ◽  
Bhushan Kapur ◽  
Joey Gareri ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Alcohol Exposure ◽  
Fatty Acid Ethyl Esters ◽  
Ethyl Esters ◽  
Fetal Alcohol Exposure ◽  
Canadian Study ◽  
Fetal Alcohol

scholarly journals Fetal Alcohol Exposure Increases Mammary Tumor Susceptibility and Alters Tumor Phenotype in Rats

2010 ◽  
Vol 34 (11) ◽  
pp. 1879-1887 ◽  
Author(s):  
Tiffany A. Polanco ◽  
Catina Crismale-Gann ◽  
Kenneth R. Reuhl ◽  
Dipak K. Sarkar ◽  
Wendie S. Cohick
Keyword(s):  
Mammary Tumor ◽  
Alcohol Exposure ◽  
Fetal Alcohol Exposure ◽  
Fetal Alcohol ◽  
Tumor Susceptibility ◽  
Tumor Phenotype

scholarly journals Fetal Alcohol Exposure: The Common Toll

2017 ◽  
Vol 05 (01) ◽  
Author(s):  
Marie R Nakhoul ◽  
Karl E Seif ◽  
Natasha Haddad ◽  
Georges E Haddad
Keyword(s):  
Alcohol Exposure ◽  
Fetal Alcohol Exposure ◽  
Fetal Alcohol ◽  
The Common

scholarly journals Sex Modifies the Effect of Genetic Risk Scores for Polycystic Ovary Syndrome on Metabolic Phenotypes

2021 ◽  
Author(s):  
Ky'Era V. Actkins ◽  
Genevieve Jean-Pierre ◽  
Melinda C. Aldrich ◽  
Digna R. Velez Edwards ◽  
Lea K. Davis
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Risk ◽  
Polycystic Ovary ◽  
Medical Center ◽  
Genetic Risk Score ◽  
Risk Scores ◽  
Ovary Syndrome ◽  
Biological Variables ◽  
Increased Risk ◽  
The Relationship

Females with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women, have an increased risk of developing metabolic disorders such as insulin resistance, obesity, and type 2 diabetes (T2D). Furthermore, while only diagnosable in females, males with a family history of PCOS can also exhibit a poor cardiometabolic profile. Therefore, we aimed to elucidate the role of sex in the relationship between PCOS and its comorbidities by conducting bidirectional genetic risk score analyses in both sexes. We conducted a phenome-wide association study (PheWAS) using PCOS polygenic risk scores (PCOSPRS) to understand the pleiotropic effects of PCOS genetic liability across 1,380 medical conditions in females and males recorded in the Vanderbilt University Medical Center electronic health record (EHR) database. After adjusting for age and genetic ancestry, we found that European descent males with higher PCOSPRS were significantly more likely to develop cardiovascular diseases than females at the same level of genetic risk, while females had a higher odds of developing T2D. Based on observed significant associations, we tested the relationship between PRS for comorbid conditions (e.g., T2D, body mass index, hypertension, etc.) and found that only PRS generated for BMI and T2D were associated with a PCOS diagnosis. We then further decomposed the T2DPRS association with PCOS by adjusting the model for measured BMI and BMIresidual (enriched for the environmental contribution to BMI). Results demonstrated that genetically regulated BMI primarily accounted for the relationship between T2DPRS and PCOS. This was further supported in a mediation analysis, which only revealed clinical BMI measurements, but not BMIresidual, as a strong mediator for both sexes. Overall, our findings show that the genetic architecture of PCOS has distinct metabolic sex differences, but these associations are only apparent when PCOSPRS is explicitly modeled. It is possible that these pathways are less explained by the direct genetic risk of metabolic traits than they are by the risk factors shared between them, which can be influenced by biological variables such as sex.

scholarly journals Long-lasting alterations to DNA methylation and ncRNAs could underlie the effects of fetal alcohol exposure in mice

2013 ◽  
Vol 6 (4) ◽  
pp. 977-992 ◽  
Author(s):  
B. I. Laufer ◽  
K. Mantha ◽  
M. L. Kleiber ◽  
E. J. Diehl ◽  
S. M. F. Addison ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Alcohol Exposure ◽  
Fetal Alcohol Exposure ◽  
Fetal Alcohol
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