Within-family heritability estimates for behavioural and disease phenotypes from 500,000 sibling pairs of diverse ancestries
Quantification of the direct effect of genetic variation on human behavioural traits is important for understanding between-individual variation in socio-economic and health outcomes but estimates of their heritability can be biased by between-family indirect genetic effects. In contrast, using within-family variation in DNA sharing is robust to most confounding factors including shared environmental effects and population stratification. Yet, accurate estimates for most traits are not available using this design, and none for non-European ancestry populations. Here, we analyse approximately 500,000 sibling pairs with diverse ancestries and obtain robust and precise heritability estimates for 14 phenotypes, including two well-studied model traits (height and BMI), five behavioural phenotypes and two common diseases. We find substantial heritability for smoking initiation (0.34 ± 0.05), alcohol consumption (0.18 ± 0.04), number of children (0.27 ± 0.11) and personality (“talk versus listen”, 0.48 ± 0.13). In addition, we estimated large heritability for two common diseases, type 2 diabetes (T2D: 0.43 ± 0.06) and asthma (0.34 ± 0.06), whose risk factors include behavioural traits. Overall, we show concordant estimates across ancestry groups and highlight a significant contribution of shared environmental effects for behaviour and T2D risk, which may have inflated between-family estimates. Altogether, our results demonstrate that substantial genetic variation underlies complex traits, common disease and exposures, that estimates are concordant across ancestries and that they are larger than has been accounted for by GWAS to date.
### Competing Interest Statement
Y.L. and J.M.G. are employed by and hold stock or stock options in 23andMe, Inc. X.W. is a former employee of 23andMe Inc. Other authors have no competing interests to declare.
### Funding Statement
L.Y. is supported by the Australian Research Council (FT220100069) and the Snow Medical Research Foundation. P.M.V. was supported by the Australian Research Council (FL180100072). D.M.E. is supported by an Australian National Health and Medical Research Council Investigator Award (2017942).
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Individuals included in this study are research participants of 23andMe, Inc., a consumer genetics and research company who were genotyped as part of the 23andMe Personal Genome Service. 23andMe participants provided informed consent and volunteered to participate in the research online, under a protocol approved by the external AAHRPP-accredited IRB, Ethical & Independent (E&I) Review Services. As of 2022, E&I Review Services is part of Salus IRB (https://www.versiticlinicaltrials.org/salusirb). In the current study, we used research-consented individuals providing self-reported phenotypes, with at least one genetically inferred full sibling also in the cohort. The total sample size of 23andMe participants analysed in the current study is 1,024,523.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
Application for data access can be submitted at <https://research.23andme.com/dataset-access/>.
