G. Abecasis, L. Cardon, and W. Cookson, A General Test of Association for Quantitative Traits in Nuclear Families, The American Journal of Human Genetics, vol.66, issue.1, pp.279-92, 2000.
DOI : 10.1086/302698

S. Antonarakis and J. Beckmann, Mendelian disorders deserve more attention, Nature Reviews Genetics, vol.3, issue.4, pp.277-82, 2006.
DOI : 10.1038/nrg1826

V. Beaumont, B. Jacotot, and J. Beaumont, Ischaemic disease in men and women with familial hypercholesterolaemia and xanthomatosis A comparative study of genetic and environmental factors in 274 heterozygous cases, Atherosclerosis, vol.24, issue.3, pp.441-450, 1976.
DOI : 10.1016/0021-9150(76)90136-2

J. Beckmann, X. Estivill, and S. Antonarakis, Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability, Nature Reviews Genetics, vol.39, issue.8, pp.639-685, 2007.
DOI : 10.1038/nrg2149

S. Blackman, R. Deering-brose, R. Mcwilliams, K. Naughton, B. Coleman et al., Relative Contribution of Genetic and Nongenetic Modifiers to Intestinal Obstruction in Cystic Fibrosis, Gastroenterology, vol.131, issue.4, pp.1030-1039, 2006.
DOI : 10.1053/j.gastro.2006.07.016

C. Bourgain, E. Genin, N. Cox, and F. Clerget-darpoux, Are genome-wide association studies all that we need to dissect the genetic component of complex human diseases?, European Journal of Human Genetics, vol.37, issue.3, pp.260-263, 2007.
DOI : 10.1038/sj.ejhg.5201753
URL : https://hal.archives-ouvertes.fr/inserm-00119120

R. Brinkman, M. Dubé, G. Rouleau, A. Orr, and M. Samuels, Human monogenic disorders ??? a source of novel drug targets, Nature Reviews Genetics, vol.20, issue.4, pp.249-60, 2006.
DOI : 10.1038/nrg1828

L. Cardon and L. Palmer, Population stratification and spurious allelic association, The Lancet, vol.361, issue.9357, pp.598-604, 2003.
DOI : 10.1016/S0140-6736(03)12520-2

S. Chanock, T. Manolio, M. Boehnke, E. Boerwinkle, D. Hunter et al., Replicating genotype???phenotype associations, Nature, vol.316, issue.7145, pp.655-60, 2007.
DOI : 10.1038/447655a

P. Charron, D. Héron, M. Gargiulo, P. Richard, O. Dubourg et al., Genetic testing and genetic counselling in hypertrophic cardiomyopathy: the French experience, Journal of Medical Genetics, vol.39, issue.10, pp.741-747, 2002.
DOI : 10.1136/jmg.39.10.741

S. Choudhry, N. Coyle, H. Tang, K. Salari, D. Lind et al., Population stratification confounds genetic association studies among Latinos, Human Genetics, vol.4, issue.11, pp.652-64, 2006.
DOI : 10.1007/s00439-005-0071-3

F. Clerget-darpoux and R. Elston, Are Linkage Analysis and the Collection of Family Data Dead? Prospects for Family Studies in the Age of Genome-Wide Association, Human Heredity, vol.64, issue.2, pp.91-97, 2007.
DOI : 10.1159/000101960
URL : https://hal.archives-ouvertes.fr/inserm-00129091

J. Delaunay, R. Wilmotte, N. Alloisio, and J. Marechal, The quiet yet dangerous alpha[LELY] allele of red cell spectrin, M.S. Med. sci, vol.11, pp.752-754, 1995.

W. Dietrich, E. Lander, J. Smith, A. Moser, K. Gould et al., Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse, Cell, vol.75, issue.4, pp.631-640, 1993.
DOI : 10.1016/0092-8674(93)90484-8

M. Drumm, M. Konstan, M. Schluchter, A. Handler, R. Pace et al., Genetic Modifiers of Lung Disease in Cystic Fibrosis, New England Journal of Medicine, vol.353, issue.14, pp.1443-53, 2005.
DOI : 10.1056/NEJMoa051469

. Encode-project-consortium, Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project, Nature, vol.447, pp.799-816, 2007.

M. Epstein, A. Allen, and G. Satten, A Simple and Improved Correction for Population Stratification in Case-Control Studies, The American Journal of Human Genetics, vol.80, issue.5, pp.921-951, 2007.
DOI : 10.1086/516842

D. Fardo, J. Celedon, B. Raby, S. Weiss, and C. Lange, On dichotomizing phenotypes in family-based association tests: quantitative phenotypes are not always the optimal choice, Genetic Epidemiology, vol.119, issue.5, pp.376-82, 2007.
DOI : 10.1002/gepi.20218

E. Feingold, Methods for Linkage Analysis of Quantitative Trait Loci in Humans, Theoretical Population Biology, vol.60, issue.3, pp.167-80, 2001.
DOI : 10.1006/tpbi.2001.1545

J. Feingold, Les g??nes modificateurs dans les maladies h??r??ditaires., m??decine/sciences, vol.16, issue.4, 2000.
DOI : 10.4267/10608/1699

J. Forissier, P. Charron, T. Du-montcel, S. Hagège, A. Isnard et al., Diagnostic accuracy of a 2D left ventricle hypertrophy score for familial hypertrophic cardiomyopathy, European Heart Journal, vol.26, issue.18, pp.1882-1888, 2005.
DOI : 10.1093/eurheartj/ehi276

T. Frayling, Genome???wide association studies provide new insights into type 2 diabetes aetiology, Nature Reviews Genetics, vol.39, issue.9, pp.657-62, 2007.
DOI : 10.1038/nrg2178

D. Futuyma, M. Sinauer, S. Gayther, J. Mangion, P. Russell et al., Evolutionary biology Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene, Nat Genet, vol.15, pp.103-108, 1997.

L. Goldfarb, R. Petersen, M. Tabaton, P. Brown, A. Leblanc et al., Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism, Science, vol.258, issue.5083, pp.806-814, 1992.
DOI : 10.1126/science.1439789

L. Gouya, J. Deybach, J. Lamoril, D. Silva, V. Beaumont et al., Modulation of the phenotype in dominant erythropoietic protoporphyria by a low expression of the normal ferrochelatase allele, Am J Hum Genet, vol.58, pp.292-301, 1996.

L. Gouya, C. Martin-schmitt, A. Robreau, F. Austerlitz, D. Silva et al., Contribution of a Common Single-Nucleotide Polymorphism to the Genetic Predisposition for Erythropoietic Protoporphyria, The American Journal of Human Genetics, vol.78, issue.1, pp.2-14, 2006.
DOI : 10.1086/498620
URL : https://hal.archives-ouvertes.fr/hal-00531080

L. Gouya, H. Puy, J. Lamoril, D. Silva, V. Grandchamp et al., Inheritance in erythropoietic protoporphyria: a common wild-type ferrochelatase allelic variant with low expression accounts for clinical manifestation, Blood, vol.93, pp.2105-2115, 1999.

H. Grüneberg, The Pathology of Development; a Study of Inherited Skeletal Disorders in Animals, 1963.

J. Haldane, The relative importance of principal and modifying genes in determining some human diseases, Journal of Genetics, vol.7, issue.2-3, pp.149-157, 1941.
DOI : 10.1007/BF02983018

J. Hall, W. Horton, H. Hauser, E. Watanabe, R. Duren et al., Ordered subset analysis in genetic linkage mapping of complex traits, Genetics Glossary. Growth, Genetics Genet Epidemiol, vol.27, pp.53-63, 1997.

R. Houlston and I. Tomlinson, Modifier genes in humans: strategies for identification, European Journal of Human Genetics, vol.6, issue.1, pp.80-88, 1998.
DOI : 10.1038/sj.ejhg.5200156

R. Klein, C. Zeiss, E. Chew, J. Tsai, R. Sackler et al., Complement Factor H Polymorphism in Age-Related Macular Degeneration, Science, vol.308, issue.5720, pp.385-394, 2005.
DOI : 10.1126/science.1109557

M. Komajda and P. Charron, A new approach for the identification of modifier genes in heart failure, The Pharmacogenomics Journal, vol.4, issue.4, pp.221-224, 2004.
DOI : 10.1038/sj.tpj.6500257

J. Li, M. Hayden, E. Almqvist, R. Brinkman, A. Durr et al., A Genome Scan for Modifiers of Age at Onset in Huntington Disease: The HD MAPS Study, The American Journal of Human Genetics, vol.73, issue.3, pp.682-689, 2003.
DOI : 10.1086/378133

J. Li, M. Hayden, S. Warby, A. Durr, P. Morrison et al., Genome-wide significance for a modifier of age at neurological onset in Huntington's Disease at 6q23-24: the HD MAPS study, BMC Medical Genetics, vol.63, issue.3, p.71, 2006.
DOI : 10.1086/302011

J. Li and J. L. , Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix, Heredity, vol.62, issue.3, pp.221-227, 2005.
DOI : 10.1002/1098-2272(200012)19:4<323::AID-GEPI4>3.0.CO;2-5

Q. Li and K. Yu, Improved correction for population stratification in genome-wide association studies by identifying hidden population structures, Genetic Epidemiology, vol.23, issue.3, pp.215-241, 2008.
DOI : 10.1002/gepi.20296

D. Luca, S. Ringquist, L. Klei, A. Lee, C. Gieger et al., On the Use of General Control Samples for Genome-wide Association Studies: Genetic Matching Highlights Causal Variants, The American Journal of Human Genetics, vol.82, issue.2, pp.453-63, 2008.
DOI : 10.1016/j.ajhg.2007.11.003

S. Lyonnet, J. Feingold, and J. Frezal, Genotype-phenotype relationshipsed) Nature encyclopedia of human genome, pp.56-63, 2003.

S. Macgregor, N. Craddock, and P. Holmans, Use of phenotypic covariates in association analysis by sequential addition of cases, European Journal of Human Genetics, vol.47, issue.5, pp.529-563, 2006.
DOI : 10.1038/sj.ejhg.5201604

J. Milet, V. Dehais, C. Bourgain, A. Jouanolle, A. Mosser et al., Common Variants in the BMP2, BMP4, and HJV Genes of the Hepcidin Regulation Pathway Modulate HFE Hemochromatosis Penetrance, The American Journal of Human Genetics, vol.81, issue.4, pp.799-807, 2007.
DOI : 10.1086/520001

J. Nadeau, Modifier genes in mice and humans, Nature Reviews Genetics, vol.343, issue.3, pp.165-174, 2001.
DOI : 10.1038/35056009

D. Nyholt, A Simple Correction for Multiple Testing for Single-Nucleotide Polymorphisms in Linkage Disequilibrium with Each Other, The American Journal of Human Genetics, vol.74, issue.4, pp.765-774, 2004.
DOI : 10.1086/383251

M. Okun and N. Thommi, Americo Negrette (1924 to 2003): Diagnosing Huntington disease in Venezuela, Neurology, vol.63, issue.2, pp.340-343, 1924.
DOI : 10.1212/01.WNL.0000129827.16522.78

H. Perdry, B. Maher, M. Babron, T. Mchenry, F. Clerget-darpoux et al., An ordered subset approach to including covariates in transmission disequilibrium The Ordered Transmission Disequilibrium Test: detection of modifier genes Principal components analysis corrects for stratification in genome-wide association studies, BMC Proceedings In press Perdry H, pp.904-913, 2006.

S. Purcell, S. Cherny, and P. Sham, Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits, Bioinformatics, vol.19, issue.1, pp.149-150, 2003.
DOI : 10.1093/bioinformatics/19.1.149

P. Richard, P. Charron, L. Carrier, C. Ledeuil, T. Cheav et al., Hypertrophic cardiomyopathy. Distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy, ACC Current Journal Review, vol.12, issue.4, pp.2227-2259, 2003.
DOI : 10.1016/S1062-1458(03)00298-8
URL : https://hal.archives-ouvertes.fr/hal-01110561

J. Rogus and A. Krolewski, Using discordant sib pairs to map loci for qualitative traits with high sibling recurrence risk, Am J Hum Genet, vol.59, pp.1376-81, 1996.

M. Schluchter, M. Konstan, M. Drumm, J. Yankaskas, and M. Knowles, Classifying Severity of Cystic Fibrosis Lung Disease Using Longitudinal Pulmonary Function Data, American Journal of Respiratory and Critical Care Medicine, vol.174, issue.7, pp.780-786, 2006.
DOI : 10.1164/rccm.200512-1919OC

D. Shattuck-eidens, M. Mcclure, J. Simard, F. Labrie, S. Narod et al., A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening, JAMA: The Journal of the American Medical Association, vol.273, issue.7, pp.535-576, 1995.
DOI : 10.1001/jama.273.7.535

W. Silvers, The Coat Colors of Mice: A Model for Mammalian Gene Action and Interaction, 1979.
DOI : 10.1007/978-1-4612-6164-3

A. Slavotinek and L. Biesecker, Genetic modifiers in human development and malformation syndromes, including chaperone proteins, Human Molecular Genetics, vol.12, issue.90001, pp.45-50, 2003.
DOI : 10.1093/hmg/ddg099

R. Spielman, R. Mcginnis, and W. Ewens, Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM), Am J Hum Genet, vol.52, pp.506-522, 1993.

P. Spirito and B. Marron, Relation between extent of left ventricular hypertrophy and occurrence of sudden cardiac death in hypertrophic cardiomyopathy, Journal of the American College of Cardiology, vol.15, issue.7, pp.1020-1027, 1990.
DOI : 10.1016/0735-1097(90)92820-R

M. Steffens, C. Lamina, T. Illig, T. Bettecken, R. Vogler et al., SNP-Based Analysis of Genetic Substructure in the German Population, Human Heredity, vol.62, issue.1, pp.20-29, 2006.
DOI : 10.1159/000095850

T. Suzuki, A. Kashiwagi, K. Mori, I. Urabe, and T. Yomo, History dependent effects on phenotypic expression of a newly emerged gene, Biosystems, vol.77, issue.1-3, pp.137-141, 2004.
DOI : 10.1016/j.biosystems.2004.05.024

A. Thakkinstian, P. Han, M. Mcevoy, W. Smith, J. Hoh et al., Systematic review and meta-analysis of the association between complementary factor H Y402H polymorphisms and age-related macular degeneration, Human Molecular Genetics, vol.15, issue.18, pp.2784-90, 2006.
DOI : 10.1093/hmg/ddl220

L. Vanscoy, S. Blackman, J. Collaco, A. Bowers, T. Lai et al., Heritability of Lung Disease Severity in Cystic Fibrosis, American Journal of Respiratory and Critical Care Medicine, vol.175, issue.10, pp.1036-1079, 2007.
DOI : 10.1164/rccm.200608-1164OC

G. Wang and T. Cooper, Splicing in disease: disruption of the splicing code and the decoding machinery, Nature Reviews Genetics, vol.16, issue.10, pp.749-761, 2007.
DOI : 10.1038/nrg2164

H. Watkins, A. Rosenzweig, D. Hwang, T. Levi, W. Mckenna et al., Characteristics and Prognostic Implications of Myosin Missense Mutations in Familial Hypertrophic Cardiomyopathy, New England Journal of Medicine, vol.326, issue.17, pp.1108-1122, 1992.
DOI : 10.1056/NEJM199204233261703

N. Wexler, J. Lorimer, J. Porter, F. Gomez, C. Moskowitz et al., Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset, Proc Natl Acad Sci, vol.101, pp.3498-503, 2004.

M. Witsch-baumgartner, I. Schwentner, M. Gruber, P. Benlian, J. Bertranpetit et al., Age and origin of major Smith-Lemli-Opitz Syndrome (SLOS) mutations in European populations Identical mutations and phenotypic variation, J Med Genet Wolf U Hum Genet, vol.100, pp.305-326, 1997.

Z. Xu, N. Kaplan, and J. Taylor, Tag SNP selection for candidate gene association studies using HapMap and gene resequencing data, European Journal of Human Genetics, vol.8, issue.10, pp.1063-70, 2007.
DOI : 10.1038/nrg1962

J. Zielenski, M. Corey, R. Rozmahel, D. Markiewicz, I. Aznarez et al., Detection of a cystic fibrosis modifier locus for meconium ileus on human chromosome 19q13, Nat Genet, vol.22, pp.128-137, 1999.