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Background  Preterm birth is a leading cause of perinatal mortality and long-term health consequences. Epigenetic mechanisms may have been at play in preterm birth survivors, and these could be persistent and detrimental to health later in life.    Methods  We performed a genome-wide DNA methylation profiling in adult twins of premature birth to identify genomic regions under differential epigenetic regulation in 144 twins with a median age of 33 years (age range 30–36).    Results  Association analysis detected three genomic regions annotated to the  SDHAP3 ,  TAGLN3  and  GSTT1  genes on chromosomes 5, 3 and 22 (FWER: 0.01, 0.02 and 0.04) respectively. These genes display strong involvement in neurodevelopmental disorders, cancer susceptibility and premature delivery. The three identified significant regions were successfully replicated in an independent sample of twins of even older age (median age 66, range 56–80) with similar regulatory patterns and nominal  p  values < 5.05e−04. Biological pathway analysis detected five significantly enriched pathways all explicitly involved in immune responses.    Conclusion  We have found novel evidence associating premature delivery with epigenetic modification of important genes/pathways and revealed that preterm birth, as an early life event, could be related to differential methylation regulation patterns observable in adults and even at high ages which could potentially mediate susceptibility to age-related diseases and adult health.    Electronic supplementary material  The online version of this article (10.1186/s13148-018-0518-8) contains supplementary material, which is available to authorized users.

Epigenetic signature of preterm birth in adult twins