Sequence variants affecting voice pitch in humans

Abstract

The genetic basis of the human vocal system is largely unknown, as are the sequence variants that give rise to individual differences in voice and speech. Here, we couple data on diversity in the sequence of the genome with voice and vowel acoustics in speech recordings from 12,901 Icelanders. We show how voice pitch and vowel acoustics vary across the life span and correlate with anthropometric, physiological, and cognitive traits. We found that voice pitch and vowel acoustics have a heritable component and discovered correlated common variants in ABCC9 that associate with voice pitch. The ABCC9 variants also associate with adrenal gene expression and cardiovascular traits. By showing that voice and vowel acoustics are influenced by genetics, we have taken important steps toward understanding the genetics and evolution of the human vocal system.

Fig. 1.. Voice pitch and vowel acoustics across the life span.

(A) Voice pitch in reading (median f_o in hertz) is plotted for males and females according to age. For each age group and sex, the bottom and top of the boxes indicate the bottom and top quartiles, the line inside the box indicates the median, the whiskers indicate the most extreme values inside 1.5 times the interquartile range, and the dots indicate values outside that range. (B) Vowel formant F₂ is plotted (in hertz) according to age and sex in the vowel [i] (similar to the vowel in English "meet"). (C) Vowel formant F₂ in vowel [ɛ] ("met"). (D) Vowel formant F₄ in vowel [u] ("boot").

Fig. 2.. Phenotypic correlations with selected voice measures.

Representative correlations (Bonferroni threshold 3.2 × 10⁻⁸) with other phenotypes for voice pitch in reading (f_o median) and voice pitch variability in reading (f_o SD) are shown. Each point with 95% CIs reflects the correlation with a phenotype, the x axis shows the phenotype, and the y axis displays the correlation coefficient (r). The direction of correlation for Trail Making Test (measured in seconds) was reversed to reflect better performance.

Fig. 3.. Association with voice pitch.

(A) Manhattan plot of the association results for voice pitch in reading (median f_o). Each variant in the genome is represented as a black or gray point and positioned according to its chromosomal position (x axis) and the −log₁₀ P value for association with voice pitch in reading (y axis). rs11046212-T is indicated with a red diamond. (B) Voice pitch in reading, presented in hertz, as a function of rs11046212-T genotype and age in males and females.

Fig. 4.. Regional plots of ABCC9 variants associated with voice pitch, pulse pressure, aortic area, and ABCC9 expression in adrenal gland.

Variants are plotted according to their genomic position (x axis) and the −log₁₀ P value for association with the phenotype (left y axis). The lead variant rs11046212-T is shown as purple; other variants are colored to reflect their correlation (LD) with the lead (those in red are highly correlated with the lead variant). Nearby genes are shown on the bottom.