Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes

• Published in: Nature communications Vol. 12; no. 1; pp. 20211 - 11
• Main Authors: Xue, Angli, Jiang, Longda, Zhu, Zhihong, Wray, Naomi R., Visscher, Peter M., Zeng, Jian, Yang, Jian
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.01.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 45/43; 631/208/205; 631/208/457; 631/208/480; 692/499; Alcohol; Alcohol Drinking - genetics; Alcohols; Behavior; Bias; Biobanks; Biological Specimen Banks; Body Mass Index; Disease; Genetic diversity; Genetic variance; Genome-wide association studies; Genome-Wide Association Study; Genomes; Humanities and Social Sciences; Humans; Mendelian Randomization Analysis; multidisciplinary; Quantitative Trait, Heritable; Science; Science (multidisciplinary); United Kingdom; United Kingdom; United Kingdom > UK
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20237-6

Genome-wide association studies (GWAS) have discovered numerous genetic variants associated with human behavioural traits. However, behavioural traits are subject to misreports and longitudinal changes (MLC) which can cause biases in GWAS and follow-up analyses. Here, we demonstrate that individuals with higher disease burden in the UK Biobank ( n = 455,607) are more likely to misreport or reduce their alcohol consumption levels, and propose a correction procedure to mitigate the MLC-induced biases. The alcohol consumption GWAS signals removed by the MLC corrections are enriched in metabolic/cardiovascular traits. Almost all the previously reported negative estimates of genetic correlations between alcohol consumption and common diseases become positive/non-significant after the MLC corrections. We also observe MLC biases for smoking and physical activities in the UK Biobank. Our findings provide a plausible explanation of the controversy about the effects of alcohol consumption on health outcomes and a caution for future analyses of self-reported behavioural traits in biobank data. Conflicting reports have found disease to sometimes be positively and sometimes negatively correlated with alcohol consumption. Here, the authors show that misreporting and reduction of alcohol consumption is associated with disease, leading to misleading associations between alcohol and disease.