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Preliminary study of genome-wide association identifies novel susceptibility genes for serum mineral elements in the Chinese Han population

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Abstract

Mineral elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe)) play important biological roles in enzymes, hormones, vitamins, and normal metabolism. The deficiency of mineral elements can lead to abnormal physiological functions. And some elements (such as lead (Pb)) are harmful to the body. We aim to identify genetic loci which can influence the serum levels of mineral elements (Cu, Zn, Ca, Mg, Fe, and Pb). Genotyping was performed using Applied Biosystems Axiom™ PMDA in 587 individuals, and 6,423,076 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study (GWAS) analysis. The association between genotype and phenotype was analyzed using mixed linear regression (additive genetic model) adjusting by age and gender combined with identical by descent (IBD) matrix. Genetic loci in BCHE-LOC105374194, DTX2P1-UPK3BP1-PMS2P11, VAT1L, LINC00908-LINC00683, LINC01310-NONE, and rs6747410 in VWA3B were identified to be associated with serum Cu element concentration (p < 5 × 10−6). ADAMTSL1 rs17229526 (p = 4.96 × 10−6) was significantly associated with serum Zn element levels. Genetic loci in LRP1B, PIGZ-MELTF, LINC01365-LINC02502, and HAPLN3 were related to serum Ca element levels (p < 5 ×1 0−6). Three SNPs in ALPK1, ASAP1-ADCY8 and IER3IP1-SKOR2 also achieved a significant association with Mg element levels (p < 5 × 10−6). TACSTD2-MYSM1, LRP1B, and ASAP1-ADCY8 showed suggestive associations with serum Fe element levels (p < 5 × 10−6). Moreover, the two most significant SNPs associated with Pb were rs304234 in CADPS-LINC00698 (p = 2.47 × 10−6) and rs12666460 in LOC101928211-GPR37 (p = 1.81 × 10−6). In summary, we reported 19 suggestive loci associated with serum mineral elements in the Chinese Han population. These findings provided new insights into the potential mechanisms regulating serum mineral elements levels.

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Acknowledgements

The authors thank all participants and volunteers in this study.

Availability of Data and Materials

All the data regarding the findings are available within the manuscript. Anyone who is interested in the information should contact the corresponding author.

Funding

This study was funded by the National Natural Science Foundation of China (No. 81660013 and No.81860015) and Key Research and Development Plan of Hainan Province (No. ZDYF2018116).

Author information

Authors and Affiliations

  1. Department of General Practice, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, #19, Xiuhua Road, Xiuying District, Haikou #19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, People’s Republic of China

    Duojian Guo, Xingwei Wei, Yutian Zhang, Mei Lin, Xiaoli Zhou, Yufei Xie, Chanyi He, Qi Lin, Ping He & Yipeng Ding

  2. Zuguan Health Center, Lingshui Li Autonomous County, Lingshui, Hainan, 572426, People’s Republic of China

    Duojian Guo

  3. Appointment Clinic Service Center, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China

    Yu Zhou

  4. Xi’an 21st Century Biological Science and Technology Co., Ltd, Xi’an, Shaanxi, 712000, People’s Republic of China

    Shanshan Zhang & Tianbo Jin

  5. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, 710069, Shaanxi, China

    Shanshan Zhang & Tianbo Jin

  6. Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, 710069, Shaanxi, China

    Shanshan Zhang & Tianbo Jin

Authors
  1. Duojian Guo
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  2. Yu Zhou
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  3. Xingwei Wei
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  5. Tianbo Jin
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  6. Yutian Zhang
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  7. Mei Lin
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  8. Xiaoli Zhou
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  9. Yufei Xie
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  10. Chanyi He
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  11. Qi Lin
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  12. Ping He
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  13. Yipeng Ding
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Contributions

Duojian Guo and Yu zhou: writing; Xingwei Wei, Shanshan Zhang, Tianbo Jin: methodology; Yutian Zhang, Mei Lin, Xiaoli Zhou: data curation; Yufei Xie, Chanyi He, Qi Lin: Sample collection; Ping He and Yipeng Ding: conceptualization.

Corresponding authors

Correspondence to Ping He or Yipeng Ding.

Ethics declarations

Ethics Approval and Consent to Participate

All of the participating cohort provided written informed consents. The protocols were approved by the institutional review boards of Hainan Affiliated Hospital of Hainan Medical University, and were in the Declaration of Helsinki.

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The authors declare no competing interests.

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Duojian Guo and Yu Zhou are co-first authors

Supplementary Information

ESM 1

(DOCX 25 kb)

ESM 2.

Locus regional plots of six loci associated with serum Cu level. (PNG 9387 kb)

High Resolution Image (TIF 13251 kb)

ESM 3.

Locus regional plots of one locus associated with serum Zn level. (PNG 1311 kb)

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ESM 4.

Locus regional plots of four loci associated with serum Ca level. (PNG 7105 kb)

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ESM 5.

Locus regional plots of three loci associated with serum Mg level. (PNG 4990 kb)

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ESM 6.

Locus regional plots of three loci associated with serum Fe level. (PNG 4853 kb)

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ESM 7.

Locus regional plots of two loci associated with serum Pb level. (PNG 3201 kb)

High Resolution Image (TIF 4631 kb)

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Guo, D., Zhou, Y., Wei, X. et al. Preliminary study of genome-wide association identifies novel susceptibility genes for serum mineral elements in the Chinese Han population. Biol Trace Elem Res 200, 2549–2555 (2022). https://doi.org/10.1007/s12011-021-02854-4

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  • DOI: https://doi.org/10.1007/s12011-021-02854-4

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