Siri Eldevik Håberg MD PhD I4C, Lyon, November 12, 2012
The Norwegian Mother & Child Cohort Study Recruitment Hospitals with < 1000 births/year Hospitals with >1000 births/year Norway 60,000 births/year Inclusion period
The cohort Number Women Men Children Pregnancies Twin-pairs1 870 Triplet trios 21 Sibships~
Data collection Mother Father Child Cord blood Ultrasound Week 18Week 30Birth6 months18 months 3, 5, 7,8 years (12/13) Blood Teeth
Inclusion 1999 – 2009 (last birth in 2010)
Biological samples MoBa: Top modern biobank – automated/manual •EDTA fullblood and plasma (frozen -86 o C) •DNA extracted from fullblood (frozen -20 o C) •Urine(frozen -20 o C ) •RNA: from cord blood (Tempus-tubes) •Milk teeth
MoBa I4C Cancer •National registries linked to MoBa –Birth registry –Cancer registry (I4C) –Prescription registry –Patient registry (hospitals) –Vaccination registry –… –Specified variables (can be extended)
Epigenetic substudy •An asthma project within MoBa –Collaboration NIEHS (USA) /NIPH(Norway) •4000 maternal samples –B vitamin metabolites (around 20 - folate etc) –SNPs in B-vitamin metabolism (around 20) –2000 have A,D,E vitamin measured •1050 (+750) children of these mothers have Illumina 450 K methylation data –(cord blood DNA)
Epigenetic findings/plans •Identified 10 genes with methylation changes present at birth in children whose mothers smoked during pregnancy –(AHRR, CYP1A1, GFI1…..) •Studies in progress: –Birth weight, asthma,… –Leukemia in children (Danish/Norwegian pilot) –other exposures/outcomes (vitamins, diet, asthma..)
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Kvalitetsoppgaver i vanlig drift Prosedyre for DNA: DNA ekstraksjon•DNA isoleres fra blod. Fordeling•Fortynnes til 100 ng/µl. •Fordeles til fem 96 brønners brett og lagres ved -20 ºC.
DNA ekstraksjon Etter DNA ekstraksjon: •Brune pelleter tas ut og ekstraheres på nytt •Eventuelle avvik kommenteres i MoBaStudy
DNA fordeling OD måling: konsentrasjon og 260/280 ratio •Konsentrasjon under 100 ng/µl bemerkes i MoBaStudy. •Konsentrasjon over 145 ng/µl fortynnes og OD måling gjentas. •Alle spesialtilfeller kommenteres i MoBaStudy. •Prøver med en 260/280 ratio utenfor 1,6-2,0. kommenteres i programmet, og isoleres på nytt. •Hver 12. prøve inkluderes i kvalitetskontrollprogrammet.