Numerous researchers have investigated the associations among methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism, homocysteine (Hcy) concentration, and hypertension. However, the results are controversial. Thus, a meta‐analysis implementing Mendelian randomization approach was conducted to examine the hypothesis that elevated Hcy concentration plausibly contributes to increased risk of hypertension. Based on several inclusion and exclusion criteria, eligible studies were selected to explore the correlation between MTHFR C677T and hypertension risk, MTHFR C677T and Hcy concentration in hypertension, and Hcy concentration and hypertension, and they were evaluated by odds ratios (ORs), effect size (ES), and standard mean difference with their corresponding 95% confidence intervals (95% CIs), respectively. Moreover, Mendelian randomization was implemented to evaluate the relationship between Hcy and hypertension. Consequently, 14 378 cases and 25 795 controls were involved in this study and the results showed that MTHFR C677T led to an elevated risk of hypertension (for T vs C: OR = 1.27, 95% CI = 1.17‐1.37; for TT vs CC: OR = 1.53, 95% CI = 1.30‐1.79). Additionally, in hypertensive subjects, the pooled Hcy concentration in individuals of TT genotype was 7.74 μmol/L (95% CI: 5.25‐10.23) greater than that in individuals of CC genotype. Moreover, the pooled Hcy concentration in hypertensive was 0.69 μmol/L (95% CI: 0.50‐0.87) greater than that in controls. The estimated causal OR associated with hypertension was 1.32 for 5 μmol/L Hcy increment. Via MTHFR C677T polymorphism, the findings in the present study demonstrated that there exists evidence on causal link between Hcy concentration and the risk of hypertension.

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The origin of tone, also known as tonogenesis , has long been a topic of great interest in language evolution and human cognition studies. Several linguistic studies of tonal languages have proposed various hypotheses that tonal origin may be related to different changes of phonological structures. However, such hypotheses have not been quantitatively tested in an evolutionary framework. Here, we conducted phylogenetic comparative analyses to assess the likelihood of different hypotheses of tonogenetic mechanisms across 106 Sino-Tibetan languages, of which approximately 70% are tonal. Our results showed that the presence of tones has a strong phylogenetic pattern and that Proto-Sino-Tibetan languages were most likely non-tonal. Our findings identified that tonal origin was strongly associated with the evolution of specific phonological structures, such as the loss of syllable-final consonants and voice quality on vowels. Furthermore, we found that tonal origin probably did not influence the diversification rates of Sino-Tibetan languages. These findings enabled us to better understand that tone arose as a compensatory mechanism for the structural organization and evolution of languages.