Genetic variants associated with motion sickness point to roles for inner ear development, neurological processes and glucose homeostasis

Abstract

Roughly one in three individuals is highly susceptible to motion sickness and yet the underlying causes of this condition are not well understood. Despite high heritability, no associated genetic factors have been discovered. Here, we conducted the first genome-wide association study on motion sickness in 80 494 individuals from the 23andMe database who were surveyed about car sickness. Thirty-five single-nucleotide polymorphisms (SNPs) were associated with motion sickness at a genome-wide-significant level (P < 5 × 10−8). Many of these SNPs are near genes involved in balance, and eye, ear and cranial development (e.g. PVRL3, TSHZ1, MUTED, HOXB3, HOXD3). Other SNPs may affect motion sickness through nearby genes with roles in the nervous system, glucose homeostasis or hypoxia. We show that several of these SNPs display sex-specific effects, with up to three times stronger effects in women. We searched for comorbid phenotypes with motion sickness, confirming associations with known comorbidities including migraines, postoperative nausea and vomiting (PONV), vertigo and morning sickness and observing new associations with altitude sickness and many gastrointestinal conditions. We also show that two of these related phenotypes (PONV and migraines) share underlying genetic factors with motion sickness. These results point to the importance of the nervous system in motion sickness and suggest a role for glucose levels in motion-induced nausea and vomiting, a finding that may provide insight into other nausea-related phenotypes like PONV. They also highlight personal characteristics (e.g. being a poor sleeper) that correlate with motion sickness, findings that could help identify risk factors or treatments.

Clinical Features, Familial History, and Migraine Precursors in Patients With Definite Vestibular Migraine: The VM‐Phenotypes Projects

“…Recent studies have emphasized how motion sickness is a common finding in the general population and it has a strong genetic contribution. 29,30 Our data are in line with a previously published work reporting a rate of migraine equivalents of 70.3% and motion sickness of 40.5% in a sample of over 1000 pediatric patients mostly with migrainous headaches. 31 Another recent review on migraine precursors reported a rate of 1.9-2.3% for cyclic vomiting, 1.7-4.1% for episodic abdominal pain, and 2-2.6% for episodic vertigo in the total pediatric population.…”

Estimating the sensorimotor components of cybersickness

“…These include genetic factors, the contribution of which should be assessed with a large sample. Several genes have recently been identified as linked to motion sickness in a full genome sequencing study (Hromatka et al, 2015), but a genome-wide approach to CS susceptibility would not be possible barring a large proportion of the population undertaking a standardised VR experience. However, it appears likely that inherited factors are a latent source of multicollinearity between the sensorimotor indices measured in our experiment, and future highpower studies will be needed in order to investigate this possibility.…”

Motion Sickness: Current Knowledge and Recent Advance

“…Finley et al for the first time reported that a single‐nucleotide polymorphism (SNP) in the α 2 ‐adrenergic receptor gene correlated with individual differences in autonomic responsiveness to provocative motion and other stressors . Recently, a genomewide association study conducted in 80,494 individuals from the 23 and Me database found that 35 SNPs in genes involved in balance function, eye, ear and cranial development, neurological processes, glucose homeostasis, or hypoxia were associated with self‐reported carsickness susceptibility . Nevertheless, it has been verified that none of these SNPs is related to vestibular function regulation.…”