craniofacial anomalies

Craniofacial anomaliesJulian LittleCanada Research Chair in Human Genome EpidemiologyDepartment of Epidemiology & Community MedicineUniversity of Ottawa

HuGENet NETWORK OF NETWORKS WORKSHOP

October 2005

OriginsWHO Human Genetics Programme, 2000Financial 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 researchto 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 meetingsNov 2000 concurrent workshops on (1) genetic basis (2) g-e interaction (3) treatmentMay 2001 preventionDec 2001 global registry

20032002

Consensus meetingsNov 2000 concurrent workshops on (1) genetic basis (2) g-e interaction (3) treatmentMay 2001 preventionDec 2001 global registryDec 2004 progress and future strategies________

Reported investigations on gene-environment interaction in aetiology of oral clefts

Variants of

Maternal exposure

Smoking

Vitamin

Alcohol

Occup

exp

Medication

Supps

A

Folate/FA

TGF

8

2

1

2

TGF3

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

TGF

TGF3

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

TGF

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

TGF

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

TGF

TGF3

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

TGF

TGF3

MSX1

BCL1

Smoking

Identifying teams

List developed from WHO reports and literature searchesAsked those who attended WHO meetings (1) about concept (2) to review list and extend if possibleContact additional teams identified

Teamswith established data and sample collections with ongoing data and sample collectionsplanning to establish data and sample collections

Numbers of teams

WHO regionEstablishedOngoingPlannedMulticountry in >1 region2 (trios and other familial)3 (trios and other familial)-AFR--1AMR8 (cc & trio)1 multicountry; 1 multistate; 12EMR--1EUR1 multicountry (trio);9 (cc & trio)1 cohortSEAR4 (cc & trio)-3

N of cases from cc studies; trios; samples; (studies)

WHO regionEstablishedOngoingPlanned>1? + > 2000 trios3 (trios and other familial)-AFR--(1)AMR1343 cc (5); 324 trios (3); >7000 samples (1) 1 multicountry; 1 multistate 2100cc but bio samp from 600 only;(2)EMR--(1)EURmulticountry 1169 trios; 1227 cc (9); 651 trios (4)1 cohortSEAR259 cc (3) & 213 trios (2)-(3)

Co-ordinationOttawaDundee (Peter Mossey)Iowa (Jeff Murray)

Funding

Other issuesDifferent designsSamplesGovernanceFurther analyses possible?Outside country?Elsewhere within country?Only in own centre?

May be overlap between cc and trio counts. Sometimes more controls than cases