Sowing the seed of mental health – The effect of paternal alcohol use before conception

PhD project (3/4 yr research project leading to independent research at the doctorate level)

Dr Luisa Zuccolo, Dr Gemma Sharp, Prof Anita Thapar


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Rationale

There is growing concern that paternal exposures before conception have been greatly neglected. Studying how these impact on future generations’ health could open new avenues for prevention-prospective fathers are not generally advised to change their behaviour. In animal studies, one of the paternal exposures showing the largest and most consistently reported effects relative to the prenatal period is alcohol, however convincing human evidence is lacking to date. In this project, we propose to investigate the relationship between pre-conception paternal alcohol use and offspring mental health, and in particular attention deficit hyperactivity disorder (ADHD).

Aims & objectives

1 Is paternal alcohol use before conception associated with offspring ADHD, and/or its brain morphology correlates?
2 Is this due to shared genetic influences?
3 Is this association robust to different causal inference methods of analyses such as Mendelian randomization, and the use of negative controls (eg non-biological fathers)?
4 Are offspring cord blood DNA methylation and ADHD structural brain correlates on the causal pathway from paternal alcohol exposure childhood ADHD?

Methods

To improve the chance of disentangling correlation from causation, we propose to use a paradigm similar to that of (lab studies of) rodent models of paternal effects: a pseudo-experimental study design (employing Mendelian randomization and other analytical approaches to improve causal inference), restricting to families with no intrauterine exposure to alcohol (like in the animal studies), focusing on early manifestation of the outcome occurring before the onset of own drinking to remove confounding by own drinking, and even earlier potential biological mediators of the effects (eg cord-blood DNA methylation, eliminating confounding by paternal drinking in the postnatal period, both set to ‘zero’ in animal studies).

References

Finegersh A, Alcohol 2015 49:461-70
Rogers JC, JAMA Psychiatry 2016 73:64-72
Chen YC, Mol Psychiatry 2017 Mar 21 -Epub ahead of print


Created on Oct. 19, 2017, 12:43 p.m.

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