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Karolinska Institutet

ABSTRACT: Organisation EGAO00000000652

PROVIDER: EGAO00000000652 | EGA |

REPOSITORIES: EGA

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Publications

DNA methylation in childhood asthma: an epigenome-wide meta-analysis.

Xu Cheng-Jian CJ Söderhäll Cilla C Bustamante Mariona M Baïz Nour N Gruzieva Olena O Gehring Ulrike U Mason Dan D Chatzi Leda L Basterrechea Mikel M Llop Sabrina S Torrent Maties M Forastiere Francesco F Fantini Maria Pia MP Carlsen Karin C Lødrup KCL Haahtela Tari T Morin Andréanne A Kerkhof Marjan M Merid Simon Kebede SK van Rijkom Bianca B Jankipersadsing Soesma A SA Bonder Marc Jan MJ Ballereau Stephane S Vermeulen Cornelis J CJ Aguirre-Gamboa Raul R de Jongste Johan C JC Smit Henriette A HA Kumar Ashish A Pershagen Göran G Guerra Stefano S Garcia-Aymerich Judith J Greco Dario D Reinius Lovisa L McEachan Rosemary R C RRC Azad Raf R Hovland Vegard V Mowinckel Petter P Alenius Harri H Fyhrquist Nanna N Lemonnier Nathanaël N Pellet Johann J Auffray Charles C van der Vlies Pieter P van Diemen Cleo C CC Li Yang Y Wijmenga Cisca C Netea Mihai G MG Moffatt Miriam F MF Cookson William O C M WOCM Anto Josep M JM Bousquet Jean J Laatikainen Tiina T Laprise Catherine C Carlsen Kai-Håkon KH Gori Davide D Porta Daniela D Iñiguez Carmen C Bilbao Jose Ramon JR Kogevinas Manolis M Wright John J Brunekreef Bert B Kere Juha J Nawijn Martijn C MC Annesi-Maesano Isabella I Sunyer Jordi J Melén Erik E Koppelman Gerard H GH

The Lancet. Respiratory medicine 20180226 5

<h4>Background</h4>DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma.<h4>Methods</h4>We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blo ...[more]

PMID: 29496485

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Project description:Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a descriptive clinical entity defined by the abrupt onset of psychiatric and somatic symptoms leading to significant loss of function. Data on well-characterized PANS patients are limited, biomarkers have yet to be identified, and a solid evidence base to guide treatment is lacking. In this study, we present our experience of a systematic evaluation of the first 45 patients included in a Swedish cohort. Methods: During the period 2014-2018, our clinic received 100 referrals regarding suspected PANS. All patients underwent a standardized psychiatric/medical evaluation by a child/adolescent psychiatrist and a clinical psychologist or a nurse. Those with severe symptoms were also assessed by a pediatric neurologist and a pediatric rheumatologist. Laboratory tests were obtained at different time points in an attempt to capture an active disease state. Results: Of the 100 referrals, 45 met strict PANS criteria and consented to participate in a long-term follow-up study. The median age at intake was 7.2 years (range 3.0-13.1) and 56% were male. Ninety-three percent fulfilled both criteria for acute/atypical onset of PANS symptoms and having had an infection in relation to onset. Sixteen percent had an onset of an autoimmune or inflammatory disorder in temporal relation to the onset of PANS-related symptoms. The most common onset symptoms were obsessive-compulsive disorder (89%), anxiety (78%), and emotional lability (71%). Twenty-four percent had a preexisting autoimmune disease (AD) and 18% a preexisting psychiatric/neuropsychiatric diagnosis. Sixty-four percent of biological relatives had at least one psychiatric disorder and 76% at least one AD or inflammatory disorder. Complement activation (37%), leukopenia (20%), positive antinuclear antibodies (17%), and elevated thyroid antibodies (11%) were the most common laboratory findings. Conclusions: In our PANS cohort, there was a strong indication of an association with AD. Further work is needed to establish whether any of the potential biomarkers identified will be clinically useful. Long-term follow-up of these patients using the Swedish national registers will enable a deeper understanding of the course of this patient group.

Dataset Information

Karolinska Institutet

Publications

DNA methylation in childhood asthma: an epigenome-wide meta-analysis.

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