Environment-specific maternal genetic effects in orofacial clefts
Bibliographic record
Abstract
Orofacial clefts (OFCs) affect approximately 1.7 of every 1000 live births worldwide, making them among the most common birth defects. For the approximately 600 babies born with OFCs each year in Canada, multidisciplinary surgical and nonsurgical care is needed until adulthood. In addition to psychological effects suffered by the affected children and their families, OFCs have been associated with increased risk of death from birth to age 55. OFCs clearly bring a substantial burden on affected individuals and their families and substantial costs to the health care system. Despite research efforts, the causes of OFCs are still largely unknown. Maternal environmental exposures in combination with maternal genetic effects can disrupt important processes involved in facial development. Hence, maternal genetic effects involved in OFC aetiology could act only or more strongly under specific environments. \n \nA GWAS data on over 2000 parent-offspring trios from the GENEVA (Gene-Environment Association Studies) Oral Clefts project found weak evidence for maternally mediated genetic effects but did not take the maternal environment into account. The overall goal of our study is to identify maternal genetic effects influencing OFC risk acting in specific environmental conditions. Our specific objectives and working hypotheses are: \n \n1.\tTo genotype 545 trios (child and parents) from two ongoing European studies (ITALCLEFT and EUROCRAN) and combine them to the publicly available GENEVA trios to perform a genome-wide association study (GWAS) of maternally mediated main genetic effects. \n2.\tTo perform a GWAS of the interaction between maternally mediated genetic effects and key environmental factors, including maternal smoking and multivitamin exposure. \n3.\tTo perform a GWAS of the interaction between maternal and child genetic effects, taking the environment into account. \n \nWe will use strict quality control procedures to combine existing and new genotype data. The ITALCLEFT and EUROCRAN samples have successfully been used to replicate OFC GWAS significant results. Maternal genetic effects and combined mother-child genetic effects will be tested using existing specialized association tests. Interactions will be assessed by stratification first. We will also extend and implement a recently proposed approach to detect joint effects among maternal variants, child variants, and maternal environmental exposures. \n \nOur research team brings together the extensive expertise in genetic epidemiology and biostatistics of the PI, Dr. Roy-Gagnon, to that of co-applicant Dr. Little, a world leader in Human Genome Epidemiology who has been studying the epidemiology of OFCs for over 15 years. Collaborators Drs. Rubini, Mossey and Steegers-Theunissen are also experts on OFCs and PIs of the European studies. \n \nOur project will be the first to investigate maternal gene-environment interactions at the genome-wide level. The environment is more easily modifiable compared to genetic factors. Our study could thus lead to important public health applications in terms of designing effective, targeted prenatal interventions in Canada and elsewhere.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.004 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.000 | 0.002 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.006 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".