Human Intelligence and Polymorphisms in the DNA Methyltransferase Genes Involved in Epigenetic Marking

被引:27
作者
Haggarty, Paul [1 ]
Hoad, Gwen [1 ]
Harris, Sarah E. [2 ]
Starr, John M. [3 ]
Fox, Helen C. [4 ]
Deary, Ian J. [5 ]
Whalley, Lawrence J. [4 ]
机构
[1] Univ Aberdeen, Rowett Inst Nutr & Hlth, Nutr & Epigenet Grp, Aberdeen, Scotland
[2] Univ Edinburgh, Med Genet Sect, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland
[3] Univ Edinburgh, Royal Victoria Hosp, Ctr Cognit Ageing & Cognit Epidemiol, Geriatr Med Unit, Edinburgh, Midlothian, Scotland
[4] Univ Aberdeen, Inst Appl Hlth Sci, Aberdeen, Scotland
[5] Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland
来源
PLOS ONE | 2010年 / 5卷 / 06期
基金
英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
DE-NOVO METHYLATION; IMPRINTED GENES; BRAIN-DEVELOPMENT; DNMT3L; DISORDERS; HOMOCYSTEINE; INHERITANCE; EXPRESSION; CHILDHOOD; MUTATIONS;
D O I
10.1371/journal.pone.0011329
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Epigenetic mechanisms have been implicated in syndromes associated with mental impairment but little is known about the role of epigenetics in determining the normal variation in human intelligence. We measured polymorphisms in four DNA methyltransferases (DNMT1, DNMT3A, DNMT3B and DNMT3L) involved in epigenetic marking and related these to childhood and adult general intelligence in a population (n = 1542) consisting of two Scottish cohorts born in 1936 and residing in Lothian (n = 1075) or Aberdeen (n = 467). All subjects had taken the same test of intelligence at age 11yrs. The Lothian cohort took the test again at age 70yrs. The minor T allele of DNMT3L SNP 11330C>T (rs7354779) allele was associated with a higher standardised childhood intelligence score; greatest effect in the dominant analysis but also significant in the additive model (coefficient = 1.40(additive); 95%CI 0.22,2.59; p = 0.020 and 1.99(dominant); 95%CI 0.55,3.43; p = 0.007). The DNMT3L C allele was associated with an increased risk of being below average intelligence (OR 1.25(additive); 95%CI 1.05,1.51; p = 0.011 and OR 1.37(dominant); 95%CI 1.11,1.68; p = 0.003), and being in the lowest 40(th) (p(additive) = 0.009; p(dominant) = 0.002) and lowest 30(th) (p(additive) = 0.004; p(dominant) = 0.002) centiles for intelligence. After Bonferroni correction for the number variants tested the link between DNMT3L 11330C>T and childhood intelligence remained significant by linear regression and centile analysis; only the additive regression model was borderline significant. Adult intelligence was similarly linked to the DNMT3L variant but this analysis was limited by the numbers studied and nature of the test and the association was not significant after Bonferroni correction. We believe that the role of epigenetics in the normal variation in human intelligence merits further study and that this novel finding should be tested in other cohorts.
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页数:6
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