PEL: an unbiased method for estimating age-dependent genetic disease risk from pedigree data unselected for family history

Autor: Catherine Bonaïti-Pellié, Violaine Planté-Bordeneuve, Catherine Bourgain, Dominique Stoppa-Lyonnet, Flora Alarcon, Marion Gauthier-Villars
Přispěvatelé: Génétique épidémiologique et structures des populations humaines (Inserm U535), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'oncogénétique, Institut Curie [Paris], Service de neurologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Université Paris Descartes - Paris 5 (UPD5), Bonaïti-Pellié, Catherine, Université Panthéon-Sorbonne (UP1) - Université Paris-Sud - Paris 11 (UP11) - École des hautes études en sciences sociales (EHESS) - Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS) - Université Panthéon-Sorbonne (UP1) - Université Paris-Sud - Paris 11 (UP11) - École des hautes études en sciences sociales (EHESS) - Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM), INSTITUT CURIE, Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Proband
maximum likelihood method
Epidemiology
Genes
BRCA2
Genes
BRCA1
Pedigree chart
[SDV.GEN] Life Sciences [q-bio]/Genetics
Amyloid Neuropathies
Ascertainment bias
Statistics
Prealbumin
risk estimation
MESH: Models
Genetic
Family history
Genetics (clinical)
Sampling bias
Likelihood Functions
0303 health sciences
MESH: Risk
030305 genetics & heredity
Age Factors
MESH: Bias (Epidemiology)
Penetrance
Pedigree
3. Good health
Phenotype
MESH: Portugal
France
Risk
MESH: Genetic Diseases
Inborn
penetrance function
MESH: Pedigree
Breast Neoplasms
Biology
MESH: Phenotype
Article
03 medical and health sciences
Bias
MESH: Prealbumin
Genetic model
Humans
030304 developmental biology
MESH: Age Factors
[SDV.GEN]Life Sciences [q-bio]/Genetics
Models
Statistical
MESH: Humans
Models
Genetic
Portugal
Genetic Diseases
Inborn
MESH: Amyloid Neuropathies
MESH: France
Risk Estimate
MESH: Likelihood Functions
Age of onset
MESH: Genes
BRCA1
MESH: Models
Statistical
MESH: Breast Neoplasms
MESH: Genes
BRCA2
Zdroj: Genetic Epidemiology
Genetic Epidemiology, Wiley, 2009, 33 (5), pp.379-85. ⟨10.1002/gepi.20390⟩
Genetic Epidemiology, 2009, 33 (5), pp.379-85. ⟨10.1002/gepi.20390⟩
Genetic Epidemiology, Wiley, 2009, 33 (5), pp.379-85. 〈10.1002/gepi.20390〉
ISSN: 0741-0395
1098-2272
DOI: 10.1002/gepi.20390⟩
Popis: International audience; Providing valid risk estimates of a genetic disease with variable age of onset is a major challenge for prevention strategies. When data are obtained from pedigrees ascertained through affected individuals, an adjustment for ascertainment bias is necessary. This article focuses on ascertainment through at least one affected and presents an estimation method based on maximum likelihood, called the Proband's phenotype exclusion likelihood or PEL for estimating age-dependent penetrance using disease status and genotypic information of family members in pedigrees unselected for family history. We studied the properties of the PEL and compared with another method, the prospective likelihood, in terms of bias and efficiency in risk estimate. For that purpose, family samples were simulated under various disease risk models and under various ascertainment patterns. We showed that, whatever the genetic model and the ascertainment scheme, the PEL provided unbiased estimates, whereas the prospective likelihood exhibited some bias in a number of situations. As an illustration, we estimated the disease risk for transthyretin amyloid neuropathy from a French sample and a Portuguese sample and for BRCA1/2 associated breast cancer from a sample ascertained on early-onset breast cancer cases.
Databáze: OpenAIRE
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