Tuesday 4th, 2017OC08 - Rehabilitation and Psychoeducation and Schizophrenia and Other Psychotic Disorders

Epigenetics in the remission of anorexia nervosa: a follow-up study of whole-genome methylation profiles

Nicolas RAMOZINSERM UMRS894, Center of Psychiatry & Neuroscience, Paris, 

France

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RAMOZ INSERM 894

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What is Anorexia Nervosa?• Anorexia nervosa (AN) characterized by restricted eating, obsessive fears of gaining weight, disturbance in the way in which one's body weight or shape and the voluntary pursuit of thinness• 2 Subtypes: Restrictive and Binge/Purging• Mortality rate of 10% per decade (undernutrition & suicide rate x23)

• Treatments have limited effectiveness

• Only 1/3 of patients evolved to remission

• Multifactorial disorder (like eating disorders), heritability ~70%

• More 250 candidate genes studied: no major gene identified

Strong epigenetic mechanims modulating the gene expression?

RAMOZ INSERM 894

Genome-wide methylation analysis: GWMA

Illumina Infinium® HumanMethylation450 BeadChipGenome-wide

480°000 sites/17900 genesLight green/red

Ratio Methylated/Unmethylated

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Design of the protocol

Each subject is its own control, like this we reduce the individual background

36 AN patients18 current AN

18 remitters> 1 Year follow-up

Time 0 GWMA Time 1 GWMA

Δ GWMA

RAMOZ INSERM 894

Differentially methylated regions (DMRs) between current AN & Remitters

Only few regions are differentially methylated

chr start end p.value fwer p.valueArea fwerArea

chr5 179740743 179741120 0.000013 0.004 0.00029 0.079

chr8 1905131 1905131 0.000044 0.013 0.008 0.781

chr1 248100345 248101009 0.00007 0.021 0.0001 0.043

chr22 39472177 39472177 0.0002 0.054 0.01 0.831chr10 72138124 72138124 0.0002 0.057 0.01 0.832chr10 49348564 49348564 0.0002 0.06 0.01 0.834

chr7 158045980 158046358 0.0002 0.07 0.0005 0.127

chr7 1948947 1948947 0.0006 0.137 0.01 0.86chr7 73245103 73245178 0.0008 0.17 0.006 0.721chr2 30669759 30669863 0.0009 0.181 0.007 0.726

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Top 10 DMPs between current AN & Remitters

Significant differences in 500 DMPs

CpG intercept f pval qval GENEcg00343092 0,0708 17,015 0,000101 0,204 TSPOcg14127927 0,1286 16,976 0,000102 0,205cg23488198 0,4391 16,968 0,000103 0,205cg14972143 0,2111 16,967 0,000103 0,205 EIF4Ecg15818671 0,1651 16,960 0,000103 0,205cg09901733 0,7545 16,958 0,000103 0,205 RPA1;SMYD4cg24120669 0,5937 16,922 0,000105 0,207 PCDHB6cg15627277 0,8422 16,902 0,000106 0,208cg17157275 0,8680 16,892 0,000106 0,208 NEURL1Bcg14221048 0,8828 16,855 0,000108 0,208

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GO Biological processes enriched by 300 genes

Calcium regulation, behavior, learning, synaptic transmission

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Conclusions• Identification of epigenetic signatures of prediction between current AN 

and Remission

• No major significant difference between actual AN patients and 

Remitters

• 2 whole-genome methylomic studies identified similar biological 

pathways enriched in genes involved in brain development and plasticity

RAMOZ INSERM 894

Acknowledgements

INSERM U894Center of Psychiatry & Neuroscience

Sainte-Anne HospitalUniversity of Paris Descartes

Dr J ClarkePr P Gorwood

INSERM U1061, CHRU MontpellierPr S Guillaume

Pr P Courtet