A genome-wide association study for melatonin secretion

Pi Hua Liu; Gwo Tsann Chuang; Chia Ni Hsiung; Wei Shun Yang; Hsiao Chia Ku; Yi Ching Lin; Yi Shun Chen; Yu Yao Huang; Chia Hung Lin; Wen Yi Li; Jou Wei Lin; Chih Neng Hsu; Juey Jen Hwang; Karen Chia Wen Liao; Meng Lun Hsieh; Hsiao Lin Lee; Chen Yang Shen; Yi Cheng Chang

doi:10.1038/s41598-022-12084-w

A genome-wide association study for melatonin secretion

Pi Hua Liu, Gwo Tsann Chuang, Chia Ni Hsiung, Wei Shun Yang, Hsiao Chia Ku, Yi Ching Lin, Yi Shun Chen, Yu Yao Huang, Chia Hung Lin, Wen Yi Li, Jou Wei Lin, Chih Neng Hsu, Juey Jen Hwang, Karen Chia Wen Liao, Meng Lun Hsieh, Hsiao Lin Lee, Chen Yang Shen, Yi Cheng Chang^*

^*此作品的通信作者

研究成果: 期刊稿件 › 文章 › 同行評審

4 引文斯高帕斯（Scopus）

摘要

Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10⁻⁷ to 3.44 × 10⁻⁶) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.

原文	英語
文章編號	8025
期刊	Scientific Reports
卷	12
發行號	1
DOIs	https://doi.org/10.1038/s41598-022-12084-w
出版狀態	已出版 - 12 2022

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© 2022, The Author(s).

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Liu, P. H., Chuang, G. T., Hsiung, C. N., Yang, W. S., Ku, H. C., Lin, Y. C., Chen, Y. S., Huang, Y. Y., Lin, C. H., Li, W. Y., Lin, J. W., Hsu, C. N., Hwang, J. J., Liao, K. C. W., Hsieh, M. L., Lee, H. L., Shen, C. Y., & Chang, Y. C. (2022). A genome-wide association study for melatonin secretion. Scientific Reports, 12(1), 文章 8025. https://doi.org/10.1038/s41598-022-12084-w

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abstract = "Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10−7 to 3.44 × 10−6) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.",

author = "Liu, {Pi Hua} and Chuang, {Gwo Tsann} and Hsiung, {Chia Ni} and Yang, {Wei Shun} and Ku, {Hsiao Chia} and Lin, {Yi Ching} and Chen, {Yi Shun} and Huang, {Yu Yao} and Lin, {Chia Hung} and Li, {Wen Yi} and Lin, {Jou Wei} and Hsu, {Chih Neng} and Hwang, {Juey Jen} and Liao, {Karen Chia Wen} and Hsieh, {Meng Lun} and Lee, {Hsiao Lin} and Shen, {Chen Yang} and Chang, {Yi Cheng}",

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doi = "10.1038/s41598-022-12084-w",

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AU - Ku, Hsiao Chia

AU - Lin, Yi Ching

AU - Chen, Yi Shun

AU - Huang, Yu Yao

AU - Lin, Chia Hung

AU - Li, Wen Yi

AU - Lin, Jou Wei

AU - Hsu, Chih Neng

AU - Hwang, Juey Jen

AU - Liao, Karen Chia Wen

AU - Hsieh, Meng Lun

AU - Lee, Hsiao Lin

AU - Shen, Chen Yang

AU - Chang, Yi Cheng

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N2 - Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10−7 to 3.44 × 10−6) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.

AB - Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10−7 to 3.44 × 10−6) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.

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A genome-wide association study for melatonin secretion

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