Genome-wide scans reveal variants at EDAR predominantly affecting hair straightness in Han Chinese and Uyghur populations

Abstract

Hair straightness/curliness is one of the most conspicuous features of human variation and is particularly diverse among populations. A recent genome-wide scan found common variants in the Trichohyalin (TCHH) gene that are associated with hair straightness in Europeans, but different genes might affect this phenotype in other populations. By sampling 2899 Han Chinese, we performed the first genome-wide scan of hair straightness in East Asians, and found EDAR (rs3827760) as the predominant gene (P = 4.67 × 10), accounting for 3.66 % of the total variance. The candidate gene approach did not find further significant associations, suggesting that hair straightness may be affected by a large number of genes with subtle effects. Notably, genetic variants associated with hair straightness in Europeans are generally low in frequency in Han Chinese, and vice versa. To evaluate the relative contribution of these variants, we performed a second genome-wide scan in 709 samples from the Uyghur, an admixed population with both eastern and western Eurasian ancestries. In Uyghurs, both EDAR (rs3827760: P = 1.92 × 10) and TCHH (rs11803731: P = 1.46 × 10) are associated with hair straightness, but EDAR (OR 0.415) has a greater effect than TCHH (OR 0.575). We found no significant interaction between EDAR and TCHH (P = 0.645), suggesting that these two genes affect hair straightness through different mechanisms. Furthermore, haplotype analysis indicates that TCHH is not subject to selection. While EDAR is under strong selection in East Asia, it does not appear to be subject to selection after the admixture in Uyghurs. These suggest that hair straightness is unlikely a trait under selection.

Towards broadening Forensic DNA Phenotyping beyond pigmentation: Improving the prediction of head hair shape from DNA

“…The binomial model based on 32 SNPs was found to predict straight vs. non-straight hair with These as well as previous findings [42][43]59,61] suggest different mechanisms of straight hair in Europeans and Asians, at least with regard to the EDAR effect. The odds ratio for EDAR rs3827760 in East Asians was previously reported at the level of about 2-2.5 in two independent studies, explaining 2-4% of the total variation in hair structure in these datasets [43,59]. Therefore, the size of the EDAR gene effect in East Asians seems to correspond with the effect of TCHH in Europeans, although a stronger effect of EDAR compared to TCHH was recently suggested by analysis of Uyghur samples, a population suggested be of 50%…”

“…Categorically, the shape category with the max (р, 1 − р) was considered as the predicted shape type. Taizhou Longitudinal) and 707 Xinjiang Uyghurs known to be of 50% European and 50% East Asian admixed ancestry [59][60] from our previous study [30], where further details on these cohorts can be found. Selection of SNP predictors was performed on hair shape that was classified into 2 categories: straight vs. non-straight, using binomial logistic regression (BLR).…”

How well do we understand the basis of classic selective sweeps in humans?

“…For example, rs1426654 in SLC24A5 accounted for 33% of the variance in skin colour in a South Asian cohort, and rs16891982 in SLC45A2 for 3.6% . rs3827760 in EDAR has been associated with a range of hair , chin and ear shape phenotypes. In other cases, associations can be more difficult to interpret: for example ACKR1 rs2814778 is associated with lower numbers of neutrophils , or LCT rs4988235 with increased BMI .…”

<p>Asian Hair: A Review of Structures, Properties, and Distinctive Disorders</p>

“…26 EDAR370A was attributable to 3.66% of the total variance. 27 On the other hand, a genome-wide analysis in Europeans found that the trichohyalin (TCHH) gene variant is accounted for their straight hair phenotypes, although it explained only around 6% of the variance. 28 The TCHH gene does not show high frequency in East Asians.…”

“…No interaction was found between these two genes, indicating their effects on hair straightness through different mechanisms. 27 In addition, recent genome-wide association studies reported the links of curl formation in African individuals to polymorphic variation in trichohyalin, a copper transporter protein CUTC, and keratin 74 of the inner root sheath. 23…”