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Acne is a common human skin disease, and globally affects ∼650 million people.1 It can be graded into 1–4 levels based on clinical examination and photographic documentation.2 Severe acne (grade IV acne of Pillsbury Grade) is characterized by widespread inflammatory lesions, such as nodules, cysts and potential scarring.2 In a recent community-based study performed in China, 5.6% of subjects were found to have severe acne, and it was more prevalent in males (7.1%) than infemales (3.4%).3 The male-biased pattern was also observed in coronary artery disease, and it was linked to Y chromosome.4, 5 Some early epidemiological studies have suggested that severe acne appeared to be present more frequently in males with XYY syndrome,6 implying a potential association between Y chromosome and severe acne.7 Nevertheless, at least to our knowledge, few efforts have been carried out to explore the role of the Y chromosome in severe acne.

Recently, we conducted a genome-wide association study (GWAS) to identify two susceptibility loci, 1q24.2 and 11p11.2, as the genetic risk factors to severe acne in the Han Chinese population.8 As GWASs generally disregard Y chromosomal SNPs (Y-SNPs), we developed a pipeline for retrieving and analyzing Y-SNPs from GWAS data.9 It provides us an opportunity to investigate the Y chromosomal variation in Han Chinese males with severe acne.

We extracted 2041 Y-SNPs of 1376 males (that is, 725 cases and 651 controls) with PLINK 1.0710 from our previous GWAS data referring to 1031 cases and 1031 controls.8 The well-matched case–control study showed minimal evidence of population stratification.8 The GWAS SNPs were genotyped by HumanOmniZhongHua-8 BeadChip (Illumina, San Diego, CA, USA). A series of efforts of quality control were performed for Y-SNP data as suggested before.9, 11 First, 297 males were removed due to high proportions of missing genotypes (>66%; Supplementary Material 1), and 1079 male samples (that is, 585 cases and 494 controls) with a call rate >85% were used in analyses. Second, 244 Y-SNPs genotyped with heterozygous alleles in the 1079 male samples were disregarded (Supplementary Material 2). Third, 25 Y-SNPs with missing genotypes in >5% of the male samples were excluded (Supplementary Material 2). Forth, 1450 Y-SNPs identified as invariant were filtered (Supplementary Material 2). Fifth, 15 Y-SNPs that occurred as recurrent mutations were not considered (Supplementary Material 3). All the above data filtering were done using the combination of PLINK 1.07 (http://pngu.mgh.harvard.edu/∼purcell/plink/),10 YTool 1.0 (http://mitotool.org/ytool/)9 and NETWORK 4.611 (http://www.fluxus-engineering.com/sharenet.htm).12

For the 307 Y-SNPs obtained after data filtering (Supplementary Material 3), we constructed the Y chromosomal haplogroup tree for 1079 male samples (Supplementary Material 4). All samples were allocated into 12 Y chromosomal (sub-)haplogroups (paragroups) spread over East Asia.13, 14 The haplogroup distribution pattern in the case and control groups is concordant with previous results about Han Chinese.15, 16 We performed statistical analyses to address the distribution of the 12 (sub-)haplogroups (paragroups) between the case and control groups (Figure 1). No statistically significant difference (P<0.05) was observed. Thus, our study provides no support for the association between Y chromosomal haplogroups and severe acne in the Han Chinese population.

Figure 1
figure 1

Y chromosomal haplogroup distribution in severe acne cases and controls in the Han Chinese population. The statistical analyses were performed by using MitoTool (http://mitotool.org/).17

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