Heikkila, K. | Search bioRxiv

bioRxiv2019

Genome-wide association study identifies 49 common genetic variants associated with handedness.

Handedness, a consistent asymmetry in skill or use of the hands, has been studied extensively because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and 32 studies from the International Handedness Consortium, we conducted the worlds largest genome-wide association study of handedness (1,534,836 right-handed, 194,198 (11.0%) left-handed and 37,637 (2.1%) ambidextrous individuals). We found 41 genetic loci associated with left-handedness and seven associated with ambidexterity at genome-wide levels of significance (P < 5x10-8). Tissue enrichment analysis implicated the central nervous system and brain tissues including the hippocampus and cerebrum in the etiology of left-handedness. Pathways including regulation of microtubules, neurogenesis, axonogenesis and hippocampus morphology were also highlighted. We found suggestive positive genetic correlations between being left-handed and some neuropsychiatric traits including schizophrenia and bipolar disorder. SNP heritability analyses indicated that additive genetic effects of genotyped variants explained 5.9% (95% CI = 5.8% - 6.0%) of the underlying liability of being left-handed, while the narrow sense heritability was estimated at 12% (95% CI = 7.2% - 17.7%). Further, we show that genetic correlation between left-handedness and ambidexterity is low (rg = 0.26; 95% CI = 0.08 - 0.43) implying that these traits are largely influenced by different genetic mechanisms. In conclusion, our findings suggest that handedness, like many other complex traits is highly polygenic, and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders that has been observed in multiple observational studies.

genetics↗

bioRxiv2017

Long-Term Leisure-Time Physical Activity and Other Health Habits as Predictors of Objectively Monitored Late-Life Physical Activity: A 40-Year Twin Study

IMPORTANCEModerate-to-vigorous physical activity (MVPA) in old age is an important indicator of good health and functional capacity enabling independent living.\n\nOBJECTIVETo investigate whether physical activity and other health habits at ages 31-48 years predict objectively measured MVPA decades later.\n\nDESIGN, SETTING, AND PARTICIPANTSThis prospective twin cohort study in Finland comprised 616 individuals (197 complete twin pairs, including 91 monozygotic pairs, born 1940-1944), who responded to baseline questionnaires in 1975, 1981, and 1990, and participated in accelerometer monitoring at follow-up (mean age, 73 years).\n\nEXPOSURESPrimary exposure was long-term leisure-time physical activity, 1975-1990 (LT-mMET index). Covariates were body mass index (BMI), work-related physical activity, smoking, heavy alcohol use and health status in 1990, and socioeconomic status.\n\nMAIN OUTCOMES AND MEASURESPhysical activity was measured with a waist-worn triaxial accelerometer (at least 10 hours per day for at least 4 days) to obtain daily mean MVPA values.\n\nRESULTSHigh baseline LT-mMET index predicted higher amounts of MVPA (increase in R2 of 6.9% after age and sex adjustment, P<.001) at follow-up. After addition of BMI to the regression model, the R2 value of the whole multivariate model was 17.2%, and with further addition of baseline smoking, socioeconomic status, and health status, the R2 increased to 20.3%. In pairwise analyses, differences in MVPA amount were seen only among twin pairs who were discordant at baseline for smoking (n=40 pairs, median follow-up MVPA 25 vs. 35 min, P=.037) or for health status (n=69 pairs, 30 vs. 44 min, P=.014). For smoking, the difference in MVPA also was seen for monozygotic pairs, but for health status, it was seen only for dizygotic pairs. Mediation analysis showed that shared genetic factors explained 82% of the correlation between LT-mMET and MVPA.\n\nCONCLUSIONS AND RELEVANCELow leisure-time physical activity at younger age, overweight, smoking, low socioeconomic status, and health problems predicted low MVPA in old age in individual-based analyses. However, based on the pairwise analyses and quantitative trait modeling, genetic factors and smoking seem to be important determinants of later-life MVPA.

epidemiology↗