A cohort study of recurrence patterns among more than 54,000 relatives of oral cleft cases in Denmark: support for the multifactorial threshold model of inheritance

Dorthe Grosen, Cécile Chevrier, Axel Skytthe, Camilla Bille, Kirsten Mølsted, Ase Sivertsen, Jeff Murray, Kaare Christensen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2010-Mar
OriginalsprogEngelsk
TidsskriftJournal of Medical Genetics
Vol/bind47
Udgave nummer3
Sider (fra-til)162-8
Antal sider6
ISSN0022-2593
DOI
StatusUdgivet - 1. mar. 2010

Fingeraftryk

Denmark
Cohort Studies
Cleft Lip
Cleft Palate
Siblings
Population

Citer dette

@article{45cfae50493f11df937d000ea68e967b,
title = "A cohort study of recurrence patterns among more than 54,000 relatives of oral cleft cases in Denmark: support for the multifactorial threshold model of inheritance",
abstract = "OBJECTIVES: To determine if the anatomical severity of oral clefting affects familial recurrence in a large population based sample. To provide reliable recurrence risk estimates for oral cleft for first, second, and third degree relatives. DESIGN: Population based cohort study. SETTING: Denmark. PARTICIPANTS: 6776 individuals affected with an oral cleft born from 1952 to 2005 and 54 229 relatives. MAIN OUTCOME MEASURES: Recurrence risk estimates for oral cleft for first, second, and third degree relatives and stratification by severity, specificity, parent of origin effect, and family size for first degree relatives. RESULTS: For cleft lip and palate probands we observed recurrence risks for first, second, and third degree relatives of respectively 3.5{\%} (95{\%} CI 3.1{\%} to 4.0{\%}), 0.8{\%} (95{\%} CI 0.6{\%} to 1.0{\%}), and 0.6{\%} (95{\%} CI 0.4{\%} to 0.8{\%}). Individuals affected by the most severe oral cleft had a significantly higher recurrence risk among both offspring and siblings, eg, the recurrence risk for siblings of a proband with isolated bilateral cleft lip with cleft palate was 4.6{\%} (95{\%} CI 3.2 to 6.1) versus 2.5{\%} (95{\%} CI 1.8 to 3.2) for a proband born with a unilateral defect. CONCLUSIONS: Anatomical severity does have an effect on recurrence in first degree relatives and the type of cleft is predictive of the recurrence type. Highly reliable estimates of recurrence have been provided for first cousins in addition to more accurate estimates for first and second degree relatives. These results and the majority of prior data continue to support a multifactorial threshold model of inheritance.",
author = "Dorthe Grosen and C{\'e}cile Chevrier and Axel Skytthe and Camilla Bille and Kirsten M{\o}lsted and Ase Sivertsen and Jeff Murray and Kaare Christensen",
year = "2010",
month = "3",
day = "1",
doi = "10.1136/jmg.2009.069385",
language = "English",
volume = "47",
pages = "162--8",
journal = "Journal of Medical Genetics",
issn = "0022-2593",
publisher = "B M J Group",
number = "3",

}

A cohort study of recurrence patterns among more than 54,000 relatives of oral cleft cases in Denmark : support for the multifactorial threshold model of inheritance. / Grosen, Dorthe; Chevrier, Cécile; Skytthe, Axel; Bille, Camilla; Mølsted, Kirsten; Sivertsen, Ase; Murray, Jeff; Christensen, Kaare.

I: Journal of Medical Genetics, Bind 47, Nr. 3, 01.03.2010, s. 162-8.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - A cohort study of recurrence patterns among more than 54,000 relatives of oral cleft cases in Denmark

T2 - support for the multifactorial threshold model of inheritance

AU - Grosen, Dorthe

AU - Chevrier, Cécile

AU - Skytthe, Axel

AU - Bille, Camilla

AU - Mølsted, Kirsten

AU - Sivertsen, Ase

AU - Murray, Jeff

AU - Christensen, Kaare

PY - 2010/3/1

Y1 - 2010/3/1

N2 - OBJECTIVES: To determine if the anatomical severity of oral clefting affects familial recurrence in a large population based sample. To provide reliable recurrence risk estimates for oral cleft for first, second, and third degree relatives. DESIGN: Population based cohort study. SETTING: Denmark. PARTICIPANTS: 6776 individuals affected with an oral cleft born from 1952 to 2005 and 54 229 relatives. MAIN OUTCOME MEASURES: Recurrence risk estimates for oral cleft for first, second, and third degree relatives and stratification by severity, specificity, parent of origin effect, and family size for first degree relatives. RESULTS: For cleft lip and palate probands we observed recurrence risks for first, second, and third degree relatives of respectively 3.5% (95% CI 3.1% to 4.0%), 0.8% (95% CI 0.6% to 1.0%), and 0.6% (95% CI 0.4% to 0.8%). Individuals affected by the most severe oral cleft had a significantly higher recurrence risk among both offspring and siblings, eg, the recurrence risk for siblings of a proband with isolated bilateral cleft lip with cleft palate was 4.6% (95% CI 3.2 to 6.1) versus 2.5% (95% CI 1.8 to 3.2) for a proband born with a unilateral defect. CONCLUSIONS: Anatomical severity does have an effect on recurrence in first degree relatives and the type of cleft is predictive of the recurrence type. Highly reliable estimates of recurrence have been provided for first cousins in addition to more accurate estimates for first and second degree relatives. These results and the majority of prior data continue to support a multifactorial threshold model of inheritance.

AB - OBJECTIVES: To determine if the anatomical severity of oral clefting affects familial recurrence in a large population based sample. To provide reliable recurrence risk estimates for oral cleft for first, second, and third degree relatives. DESIGN: Population based cohort study. SETTING: Denmark. PARTICIPANTS: 6776 individuals affected with an oral cleft born from 1952 to 2005 and 54 229 relatives. MAIN OUTCOME MEASURES: Recurrence risk estimates for oral cleft for first, second, and third degree relatives and stratification by severity, specificity, parent of origin effect, and family size for first degree relatives. RESULTS: For cleft lip and palate probands we observed recurrence risks for first, second, and third degree relatives of respectively 3.5% (95% CI 3.1% to 4.0%), 0.8% (95% CI 0.6% to 1.0%), and 0.6% (95% CI 0.4% to 0.8%). Individuals affected by the most severe oral cleft had a significantly higher recurrence risk among both offspring and siblings, eg, the recurrence risk for siblings of a proband with isolated bilateral cleft lip with cleft palate was 4.6% (95% CI 3.2 to 6.1) versus 2.5% (95% CI 1.8 to 3.2) for a proband born with a unilateral defect. CONCLUSIONS: Anatomical severity does have an effect on recurrence in first degree relatives and the type of cleft is predictive of the recurrence type. Highly reliable estimates of recurrence have been provided for first cousins in addition to more accurate estimates for first and second degree relatives. These results and the majority of prior data continue to support a multifactorial threshold model of inheritance.

U2 - 10.1136/jmg.2009.069385

DO - 10.1136/jmg.2009.069385

M3 - Journal article

C2 - 19752161

VL - 47

SP - 162

EP - 168

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 3

ER -