Robert A. Philibert, Steven R.H. Beach, Tracy D. Gunter, Gene H. Brody, Anup Madan, Meg Gerrard

Prior work using lymphoblast DNA prepared from 192 subjects from the Iowa Adoption Studies (IAS) demonstrated that decreased MAOA promoter methylation was associated with lifetime symptom count for nicotine dependence (ND) and provided suggestive evidence that the amount of methylation is genotype dependent. In the current investigation, we replicate and extend these prior findings in three ways using another 289 IAS subjects and the same methodologies. First, we show that methylation is dependent on current smoking status. Second, we introduce a factor analytic approach to DNA methylation, highlighting three distinct regions of the promoter that may function in somewhat different ways for males and females. Third, we directly compare the methylation signatures in DNA prepared from whole blood and lymphoblasts from a subset of these subjects and provide suggestive evidence favoring the use of lymphoblast DNA. We conclude that smoking reliably decreases MAOA methylation, but exact characterization of effects on level of methylation depend on genotype, smoking history, current smoking status, gender, and region of the promoter-associated CpG Island examined.