REFERENCES
1. Visscher PM, Wray NR, Zhang Q, et al. 10 Years of GWAS discovery: biology, function, and translation. Am J Hum Genet 2017;101:5-22.
2. Li S, Tollefsbol TO. DNA methylation methods: global DNA methylation and methylomic analyses. Methods 2021;187:28-43.
4. Kim JT, Li VL, Terrell SM, Fischer CR, Long JZ. Family-wide annotation of enzymatic pathways by parallel in vivo metabolomics. Cell Chem Biol 2019;26:1623-1629.e3.
5. Sanchez-Mut JV, Glauser L, Monk D, Gräff J. Comprehensive analysis of PM20D1 QTL in Alzheimer’s disease. Clin Epigenetics 2020;12:20.
6. Sanchez-Mut JV, Heyn H, Silva BA, et al. PM20D1 is a quantitative trait locus associated with Alzheimer’s disease. Nat Med 2018;24:598-603.
7. Wang Q, Chen Y, Readhead B, et al. Longitudinal data in peripheral blood confirm that PM20D1 is a quantitative trait locus (QTL) for Alzheimer’s disease and implicate its dynamic role in disease progression. Clin Epigenetics 2020;12:189.
8. Coto-Vílchez C, Martínez-Magaña JJ, Mora-Villalobos L, et al. Genome-wide DNA methylation profiling in nonagenarians suggests an effect of PM20D1 in late onset Alzheimer’s disease. CNS Spectr 2021:1-27.
9. Long JZ, Svensson KJ, Bateman LA, et al. The secreted enzyme PM20D1 regulates lipidated amino acid uncouplers of mitochondria. Cell 2016;166:424-35.
10. Long JZ, Roche AM, Berdan CA, et al. Ablation of PM20D1 reveals N-acyl amino acid control of metabolism and nociception. Proc Natl Acad Sci USA 2018;115:E6937-45.
11. Schaum N, Karkanias J, Neff NF, et al. Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature 2018;562:367-72.
12. GTEx portal. Available from: https://gtexportal.org/home/gene/PM20D1 [Last accessed on 12 August 2022].
13. HBT - Human Brain Transcriptome. Available from: https://hbatlas.org/ [Last accessed on 12 August 2022].
14. Brain RNA-Seq. Available from: http://brainrnaseq.org/ [Last accessed on 12 August 2022].
15. Velmeshev D, Schirmer L, Jung D, et al. Single-cell genomics identifies cell type-specific molecular changes in autism. Science 2019;364:685-9.
16. Kim JT, Jedrychowski MP, Wei W, et al. A Plasma protein network regulates PM20D1 and N-Acyl amino acid bioactivity. Cell Chem Biol 2020;27:1130-1139.e4.
17. Hanuš L, Shohami E, Bab I, Mechoulam R. N-Acyl amino acids and their impact on biological processes. Biofactors 2014;40:381-8.
18. Milman G, Maor Y, Abu-Lafi S, et al. N-arachidonoyl L-serine, an endocannabinoid-like brain constituent with vasodilatory properties. Proc Natl Acad Sci USA 2006;103:2428-33.
19. Tosini G, Ye K, Iuvone PM. N-acetylserotonin: neuroprotection, neurogenesis, and the sleepy brain. Neuroscientist 2012;18:645-53.
20. Rimmerman N, Bradshaw HB, Hughes HV, et al. N-palmitoyl glycine, a novel endogenous lipid that acts as a modulator of calcium influx and nitric oxide production in sensory neurons. Mol Pharmacol 2008;74:213-24.
21. Huang SM, Bisogno T, Petros TJ, et al. Identification of a new class of molecules, the arachidonyl amino acids, and characterization of one member that inhibits pain. J Biol Chem 2001;276:42639-44.
22. Tan B, O’Dell DK, Yu YW, et al. Identification of endogenous acyl amino acids based on a targeted lipidomics approach. J Lipid Res 2010;51:112-9.
23. Lin H, Long JZ, Roche AM, et al. Discovery of hydrolysis-resistant isoindoline N-Acyl amino acid analogues that stimulate mitochondrial respiration. J Med Chem 2018;61:3224-30.
24. Keipert S, Kutschke M, Ost M, et al. Long-term cold adaptation does not require FGF21 or UCP1. Cell Metab 2017;26:437-446.e5.
25. Gao Y, Shabalina IG, Braz GRF, Cannon B, Yang G, Nedergaard J. Establishing the potency of N-acyl amino acids versus conventional fatty acids as thermogenic uncouplers in cells and mitochondria from different tissues. Biochim Biophys Acta Bioenerg 2022;1863:148542.
26. Mookerjee SA, Divakaruni AS, Jastroch M, Brand MD. Mitochondrial uncoupling and lifespan. Mech Ageing Dev 2010;131:463-72.
27. Brand M. Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exper Gerontol 2000;35:811-20.
28. Zaninovich ÁA. Role of the uncoupling proteins UCP1, UCP2 and UCP3 in energy balance, type 2 diabetes and obesity: synergism with the thyroid. Med B Aires 2005;65:163-9.
29. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 2005;39:359-407.
30. Papa S, Skulachev VP. Reactive oxygen species, mitochondria, apoptosis and aging. In: Gellerich FN, Zierz S, editors. Detection of mitochondrial diseases. Boston: Springer; 1997. pp. 305-19.
31. Brand MD, Affourtit C, Esteves TC, et al. Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med 2004;37:755-67.
32. Kokoszka JE, Waymire KG, Levy SE, et al. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 2004;427:461-5.
33. Cobley JN, Fiorello ML, Bailey DM. 13 reasons why the brain is susceptible to oxidative stress. Redox Biol 2018;15:490-503.
34. consortium. human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 2015;348:648-60.
36. Benson KK, Hu W, Weller AH, et al. Natural human genetic variation determines basal and inducible expression of PM20D1, an obesity-associated gene. Proc Natl Acad Sci USA 2019;116:23232-42.
37. Cibulka M, Brodnanova M, Grendar M, et al. Alzheimer’s disease-associated SNP rs708727 in SLC41A1 may increase risk for parkinson’s disease: report from enlarged slovak study. Int J Mol Sci 2022;23:1604.
38. Greenawalt DM, Dobrin R, Chudin E, et al. A survey of the genetics of stomach, liver, and adipose gene expression from a morbidly obese cohort. Genome Res 2011;21:1008-16.
39. Gunasekara CJ, Scott CA, Laritsky E, et al. A genomic atlas of systemic interindividual epigenetic variation in humans. Genome Biol 2019;20:105.
40. Nica AC, Parts L, Glass D, et al. The architecture of gene regulatory variation across multiple human tissues: the MuTHER study. PLoS Genet 2011;7:e1002003.
41. Civelek M, Wu Y, Pan C, et al. Genetic regulation of adipose gene expression and cardio-metabolic traits. Am J Hum Genet 2017;100:428-43.
42. Karczewski KJ, Francioli LC, Tiao G, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 2020;581:434-43.
43. Heyn H, Moran S, Hernando-Herraez I, et al. DNA methylation contributes to natural human variation. Genome Res 2013;23:1363-72.
44. Li QS, Vasanthakumar A, Davis JW, et al. Association of peripheral blood DNA methylation level with Alzheimer’s disease progression. Clin Epigenetics 2021;13:191.
45. Pérez RF, Alba-Linares JJ, Tejedor JR, et al. Blood DNA methylation patterns in older adults with evolving dementia. J Gerontol A Biol Sci Med Sci 2022:glac068.
46. Kim B, Choi Y, Kim HS, Im HI. Methyl-CpG binding protein 2 in alzheimer dementia. Int Neurourol J 2019;23:S72-81.
47. Feinberg AP, Irizarry RA, Fradin D, et al. Personalized epigenomic signatures that are stable over time and covary with body mass index. Sci Transl Med 2010;2:49ra67.
48. Larrick JW, Larrick JW, Mendelsohn AR. Uncoupling mitochondrial respiration for diabesity. Rejuvenation Res 2016;19:337-40.
50. Yang R, Hu Y, Lee CH, et al. PM20D1 is a circulating biomarker closely associated with obesity, insulin resistance and metabolic syndrome. Eur J Endocrinol 2021;186:151-61.
51. Yengo L, Sidorenko J, Kemper KE, et al. Meta-analysis of genome-wide association studies for height and body mass index in ~700000 individuals of European ancestry. Hum Mol Genet 2018;27:3641-9.
52. Noronha NY, Barato M, Sae-lee C, et al. Novel Zinc-related differentially methylated regions in leukocytes of women with and without obesity. Front Nutr 2022;9:785281.
53. Satake W, Nakabayashi Y, Mizuta I, et al. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson’s disease. Nat Genet 2009;41:1303-7.
54. Yan Y, Tian J, Mo X, et al. Genetic variants in the RAB7L1 and SLC41A1 genes of the PARK16 locus in chinese parkinson’s disease patients. Int J Neurosci 2011;121:632-6.
55. Tucci A, Nalls MA, Houlden H, et al. Genetic variability at the PARK16 locus. Eur J Hum Genet 2010;18:1356-9.
56. Parkinson’s Disease Genomics Consortium (IPDGC); Wellcome Trust Case Control Consortium 2 (WTCCC2). A two-stage meta-analysis identifies several new loci for Parkinson’s disease. PLoS Genet 2011;7:e1002142.
57. Rudakou U, Yu E, Krohn L, et al. Targeted sequencing of Parkinson’s disease loci genes highlights SYT11, FGF20 and other associations. Brain 2021;144:462-72.
58. Gan-Or Z, Bar-Shira A, Dahary D, et al. Association of sequence alterations in the putative promoter of RAB7L1 with a reduced parkinson disease risk. Arch Neurol 2012;69:105-10.
59. Kolisek M, Sponder G, Mastrototaro L, et al. Substitution p.A350V in Na+/Mg2+ exchanger SLC41A1, potentially associated with Parkinson’s disease, is a gain-of-function mutation. PLoS One 2013;8:e71096.
60. Lin CH, Wu YR, Chen WL, et al. Variant R244H in Na+/Mg2+ exchanger SLC41A1 in Taiwanese Parkinson’s disease is associated with loss of Mg2+ efflux function. Parkinsonism Relat Disord 2014;20:600-3.
61. Bai Y, Dong L, Huang X, Zheng S, Qiu P, Lan F. Associations of rs823128, rs1572931, and rs823156 polymorphisms with reduced Parkinson’s disease risks. Neuroreport 2017;28:936-41.
62. Singh S, Seth PK. Functional association between NUCKS1 gene and Parkinson disease: A potential susceptibility biomarker. Bioinformation 2019;15:548-56.
63. Pihlstrøm L, Rengmark A, Bjørnarå KA, et al. Fine mapping and resequencing of the PARK16 locus in Parkinson’s disease. J Hum Genet 2015;60:357-62.
64. Nalls MA, Pankratz N, Lill CM, et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet 2014;46:989-93.
65. Hauser DN, Hastings TG. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease and monogenic parkinsonism. Neurobiol Dis 2013;51:35-42.
66. Subramaniam SR, Chesselet MF. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog Neurobiol 2013;106-107:17-32.
67. Mann VM, Cooper JM, Daniel SE, et al. Complex I, iron, and ferritin in Parkinson’s disease substantia nigra. Ann Neurol 1994;36:876-81.
68. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD. Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 1990;54:823-7.
69. González-Rodríguez P, Zampese E, Stout KA, et al. Disruption of mitochondrial complex I induces progressive parkinsonism. Nature 2021;599:650-6.
70. Votyakova TV, Reynolds IJ. Ca2+-induced permeabilization promotes free radical release from rat brain mitochondria with partially inhibited complex I. J Neurochem 2005;93:526-37.
71. Koopman WJ, Verkaart S, Visch HJ, et al. Inhibition of complex I of the electron transport chain causes O2-mediated mitochondrial outgrowth. Am J Physiol Cell Physiol 2005;288:C1440-50.
73. Hastings TG. Enzymatic oxidation of dopamine: the role of prostaglandin H synthase. J Neurochem 1995;64:919-24.
74. Berman SB, Hastings TG. Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson’s disease. J Neurochem 1999;73:1127-37.
75. Buc-Calderon P, Roberfroid M. Increase in the survival time of mice exposed to ionizing radiation by a new class of free radical scavengers. Experientia 1990;46:708-10.
76. Suzen S, Gurkok G, Coban T. Novel N-acyl dehydroalanine derivatives as antioxidants: studies on rat liver lipid peroxidation levels and DPPH free radical scavenging activity. J Enzyme Inhib Med Chem 2006;21:179-85.
77. Chang KH, Chen CM, Chen YC, et al. Association between PARK16 and Parkinson’s disease in the Han Chinese population: a meta-analysis. Neurobiol Aging 2013;34:2442.e5-9.
78. Tan EK, Kwok HH, Tan LC, et al. Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus. Neurology 2010;75:508-12.
79. Yan YP, Mo XY, Tian J, et al. An association between the PARK16 locus and Parkinson’s disease in a cohort from eastern China. Parkinsonism Relat Disord 2011;17:737-9.
80. Simón-Sánchez J, Schulte C, Bras JM, et al. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat Genet 2009;41:1308-12.
81. Deng X, Xiao B, Allen JC, et al. Parkinson’s disease GWAS-linked Park16 carriers show greater motor progression. J Med Genet 2019;56:765-8.
82. Henderson AR, Wang Q, Meechoovet B, et al. DNA methylation and expression profiles of whole blood in parkinson’s disease. Front Genet 2021;12:640266.
83. Goldstein O, Gana-Weisz M, Casey F, et al. PARK16 locus: differential effects of the non-coding rs823114 on Parkinson’s disease risk, RNA expression, and DNA methylation. J Genet Genomics 2021;48:341-5.
84. Meireles J, Massano J. Cognitive impairment and dementia in Parkinson’s disease: clinical features, diagnosis, and management. Front Neurol 2012;3:88.
85. Hanagasi HA, Tufekcioglu Z, Emre M. Dementia in Parkinson’s disease. J Neurol Sci 2017;374:26-31.
86. Gunawardhana LP, Baines KJ, Mattes J, Murphy VE, Simpson JL, Gibson PG. Differential DNA methylation profiles of infants exposed to maternal asthma during pregnancy. Pediatr Pulmonol 2014;49:852-62.
87. Langie SAS, Szarc vel Szic K, Declerck K, et al. Whole-genome saliva and blood DNA methylation profiling in individuals with a respiratory allergy. PLoS ONE 2016;11:e0151109.
88. Imran S, Neeland MR, Koplin J, et al. Epigenetic programming underpins B-cell dysfunction in peanut and multi-food allergy. Clin Transl Immunol 2021;10:e1324.
89. Li X, Zhao X, Xing J, et al. Different epigenome regulation and transcriptome expression of CD4+ and CD8+ T cells from monozygotic twins discordant for psoriasis. Australas J Dermatol 2020;61:e388-94.
90. Maltby VE, Lea RA, Sanders KA, et al. Differential methylation at MHC in CD4+ T cells is associated with multiple sclerosis independently of HLA-DRB1. MHC 2017;9:71.
91. Suderman M, Borghol N, Pappas JJ, et al. Childhood abuse is associated with methylation of multiple loci in adult DNA. BMC Med Genomics 2014;7:13.
92. Gao Y, Qimuge NR, Qin J, et al. Acute and chronic cold exposure differentially affects the browning of porcine white adipose tissue. Animal 2018;12:1435-41.
93. Sun Q, Gao Y, Yang J, Lu J, Feng W, Yang W. Mendelian randomization analysis identified potential genes pleiotropically associated with polycystic ovary syndrome. Reprod Sci 2022;29:1028-37.
94. Guay SP, Brisson D, Mathieu P, Bossé Y, Gaudet D, Bouchard L. A study in familial hypercholesterolemia suggests reduced methylomic plasticity in men with coronary artery disease. Epigenomics 2015;7:17-34.
95. Huang X, He P, Wu L. Clinical significance of peptidase M20 domain containing 1 ii patients with carotid atherosclerosis. Arq Bras Cardiol ;2022:S0066-782X2022005005206.
96. Gómez-Úriz AM, Milagro FI, Mansego ML, et al. Obesity and ischemic stroke modulate the methylation levels of KCNQ1 in white blood cells. Hum Mol Genet 2015;24:1432-40.
97. Song MA, Brasky TM, Marian C, et al. Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women. Epigenetics 2015;10:1177-87.
98. Castro de Moura M, Davalos V, Planas-Serra L, et al. Epigenome-wide association study of COVID-19 severity with respiratory failure. EBioMedicine 2021;66:103339.
99. Goldmann T, Schmitt B, Müller J, et al. DNA methylation profiles of bronchoscopic biopsies for the diagnosis of lung cancer. Clin Epigenetics 2021;13:38.
100. Revill K, Wang T, Lachenmayer A, et al. Genome-wide methylation analysis and epigenetic unmasking identify tumor suppressor genes in hepatocellular carcinoma. Gastroenterology 2013;145:1424-35.e1.
101. Huang J, Liu Z, Sun Y, et al. Use of methylation profiling to identify significant differentially methylated genes in bone marrow mesenchymal stromal cells from acute myeloid leukemia. Int J Mol Med 2018;41:679-86.
102. Chidambaran V, Zhang X, Pilipenko V, et al. Methylation quantitative trait locus analysis of chronic postsurgical pain uncovers epigenetic mediators of genetic risk. Epigenomics 2021;13:613-30.
