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*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

3 Scopus citations

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.

Original languageEnglish
Article number8025
JournalScientific Reports
Volume12
Issue number1
DOIs
StatePublished - 12 2022

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