Assessing the contribution of genetic nurture to refractive error

UK Biobank Eye and Vision Consortium

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Parents pass on both their genes and environment to offspring, prompting debate about the relative importance of nature versus nurture in the inheritance of complex traits. Advances in molecular genetics now make it possible to quantify an individual's genetic predisposition to a trait via his or her 'polygenic score'. However, part of the risk captured by an individual's polygenic score may actually be attributed to the genotype of their parents. In the most well-studied example of this indirect 'genetic nurture' effect, about half the genetic contribution to educational attainment was found to be attributed to parental alleles, even if those alleles were not inherited by the child. Refractive errors, such as myopia, are a common cause of visual impairment and pose high economic and quality-of-life costs. Despite strong evidence that refractive errors are highly heritable, the extent to which genetic risk is conferred directly via transmitted risk alleles or indirectly via the environment that parents create for their children is entirely unknown. Here, an instrumental variable analysis in 1944 pairs of adult siblings from the United Kingdom was used to quantify the proportion of the genetic risk ('single nucleotide polymorphism (SNP) heritability') of refractive error contributed by genetic nurture. We found no evidence of a contribution from genetic nurture: non-within-family SNP-heritability estimate = 0.213 (95% confidence interval 0.134-0.310) and within-family SNP-heritability estimate = 0.250 (0.152-0.372). Our findings imply the genetic contribution to refractive error is principally an intrinsic effect from alleles transmitted from parents to offspring.

Original languageEnglish
Pages (from-to)1226-1232
Number of pages7
JournalEuropean Journal of Human Genetics
Volume30
Issue number11
Early online date27 May 2022
DOIs
Publication statusPublished - 1 Nov 2022

Bibliographical note

Funding Information:
This research has been conducted using the UK Biobank Resource (application #17351). UK Biobank was established by the Wellcome Trust; the UK Medical Research Council; the Department for Health (London, UK); Scottish Government (Edinburgh, UK); and the Northwest Regional Development Agency (Warrington, UK). It also received funding from the Welsh Assembly Government (Cardiff, UK); the British Heart Foundation; and Diabetes UK. Collection of eye and vision data was supported by The Department for Health through an award made by the NIHR to the Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, and UCL Institute of Ophthalmology, London, United Kingdom (grant no. BRC2_009). Additional support was provided by The Special Trustees of Moorfields Eye Hospital, London, United Kingdom (grant no. ST 12 09). Data analysis was carried out using the HAWK computing cluster, maintained by Supercomputing Wales and Cardiff University ARCCA. This work was supported by the Welsh Government and Fight for Sight (Ref: 24WG201) to JAG and CW; NIH Grant R37MH107649–07S1 and by Research Council of Norway (NRC) Grant No. 288083 to TZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funding Information:
This research has been conducted using the UK Biobank Resource (application #17351). UK Biobank was established by the Wellcome Trust; the UK Medical Research Council; the Department for Health (London, UK); Scottish Government (Edinburgh, UK); and the Northwest Regional Development Agency (Warrington, UK). It also received funding from the Welsh Assembly Government (Cardiff, UK); the British Heart Foundation; and Diabetes UK. Collection of eye and vision data was supported by The Department for Health through an award made by the NIHR to the Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, and UCL Institute of Ophthalmology, London, United Kingdom (grant no. BRC2_009). Additional support was provided by The Special Trustees of Moorfields Eye Hospital, London, United Kingdom (grant no. ST 12 09). Data analysis was carried out using the HAWK computing cluster, maintained by Supercomputing Wales and Cardiff University ARCCA. This work was supported by the Welsh Government and Fight for Sight (Ref: 24WG201) to JAG and CW; NIH Grant R37MH107649–07S1 and by Research Council of Norway (NRC) Grant No. 288083 to TZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2022, The Author(s).

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