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Craniofacial anomalies. HuGENet NETWORK OF NETWORKS WORKSHOP October 2005. Julian Little Canada Research Chair in Human Genome Epidemiology Department of Epidemiology & Community Medicine University of Ottawa. Origins. WHO Human Genetics Programme, 2000 Financial support from NIDCR (US) - PowerPoint PPT Presentation
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Craniofacial anomalies
Julian LittleCanada Research Chair in Human Genome EpidemiologyDepartment of Epidemiology & Community MedicineUniversity of Ottawa
HuGENet NETWORK OF NETWORKS WORKSHOP
October 2005
Origins
• WHO Human Genetics Programme, 2000
• Financial support from NIDCR (US)
• Five-year project designed to take forward international strategy on craniofacial anomalies
Objectives of WHO project
• to develop an international network for consensus building, planning and development for international collaborative biomedical, epidemiological and behavioural studies in the core areas of craniofacial anomalies research
• to create a directory of research resources in craniofacial anomalies.
• to create the International Database on Craniofacial Anomalies (CFA)
Core areas
• genetic basis of CFA
• gene-environment interactions involved in CFA
• prevention of CFA
• optimal treatment of CFA
Consensus meetings
• Nov 2000 – concurrent workshops on (1) genetic basis (2) g-e interaction (3) treatment
• May 2001 – prevention
• Dec 2001 – global registry
20032002
Consensus meetings
• Nov 2000 – concurrent workshops on (1) genetic basis (2) g-e interaction (3) treatment
• May 2001 – prevention
• Dec 2001 – global registry
• Dec 2004 – progress and future strategies________
Reported investigations on gene-environment interaction in aetiology of oral clefts
Maternal exposure Smoking Vitamin Alcohol Occup
exp Medication
Variants of
Supps A Folate/FA
TGFα 8 2 1 2 TGFβ3 4 2 MSX1 3 2 BCL3 1 CYP1A1 1 EPHX1 1 GSTM1 1 1 GSTT1 1 1 NAT1 1 1 1 NAT2 2 1 1 RARA 1 1 MTHFR 2 2 RFC 1
Gene-environment interaction and oral clefts: data and sample collections
Area, period (ref)
Design Genotyping of
CL(P) n≤
CP n≤
Variants reported
Maternal exposures reported
Denmark, 1991-4 (Christensen et al., 1999; Mitchell et al., 2001, 2003)
Case- control
Infant 233 83 TGFα TGFβ3 MSX1 RARA
Smoking Alcohol Vitamins Liver
Netherlands, 1997-2000 (van Rooij et al., 2001, 2002, 2003)
Case- control
Infant & maternal
146 n.s. CYP1A1 GSTT1 NAT2 MTHFR
Smoking Medications FA Folate
Norway, 1996-8 (Jugessur et al., 2003a,b)
Case- parent trio
Infant, maternal, paternal
173 88 TGFα MTHFR
Smoking Alcohol Vitamins FA
USA, California, 1987-9 (Shaw et al., 1996, 1998a,b, 1999, 2003a, b; Lammer et al., 2004a,b ; Hartsfield et al., 2001)
Case- control
Infant 447 215 TGFα EPHX1 GSTM1 GSTT1 NAT1/2 MHFR RFC
Smoking (& P) Vitamins 13 occupational Chemical groups
USA, Iowa, 1987-94 (Romitti et al., 1999)
Case- control
Infant 154 60 TGFα TGFβ3 MSX1
Smoking Alcohol
USA, Maryland, 1984-92 (Hwang et al., 1995; Beaty et al., 1997, 2002; Maestri et al., 1997)
Case- control & trio
Infant, maternal, paternal
186 83 TGFα TGFβ3 MSX1 BCL1
Smoking
Identifying teams
• List developed from WHO reports and literature searches• Asked those who attended WHO meetings (1) about concept (2) to review list
and extend if possible• Contact additional teams identified
Teams1.with established data and sample collections
2.with ongoing data and sample collections
3.planning to establish data and sample collections
WHO region Established Ongoing Planned
Multicountry in >1 region
2 (trios and other familial)
3 (trios and other familial)
-
AFR - - 1
AMR 8 (cc & trio) 1 multicountry; 1 multistate; 1
2
EMR - - 1
EUR 1 multicountry (trio);
9 (cc & trio)
1 cohort
SEAR 4 (cc & trio) - 3
Numbers of teams
WHO region
Established Ongoing Planned
>1 ? + > 2000 trios 3 (trios and other familial)
-
AFR - - (1)
AMR 1343 cc (5); 324 trios (3); >7000 samples (1)
1 multicountry; 1 multistate 2100cc but
bio samp from 600 only;
(2)
EMR - - (1)
EUR multicountry 1169 trios; 1227 cc (9); 651 trios (4)
1 cohort
SEAR 259 cc (3) & 213 trios (2) - (3)
N of cases from cc studies; trios; samples; (studies)………
Co-ordination
• Ottawa• Dundee (Peter Mossey)• Iowa (Jeff Murray)
Funding
Other issues
• Different designs• Samples
– Governance– Further analyses possible?
• Outside country?
• Elsewhere within country?
• Only in own centre?