BACKGROUND: Less than 20  % of @entity0 @entity1 who undergo genetic testing for @entity5345 and @entity2674 carry a pathogenic mutation in one of these two genes. The GENESIS (GENE SISter) study was designed to identify new @entity0 susceptibility genes in @entity1 attending @entity5 genetics clinics and with no @entity5345 /2 mutation. METHODS: The study involved the French national network of family @entity5 clinics. It was based on enrichment in genetic factors of the recruited population through case selection relying on familial criteria, but also on the consideration of environmental factors and endophenotypes like mammary density or @entity5 characteristics to assess potential genetic heterogeneity. One of the initial aims of GENESIS was to recruit affected sibpairs. Siblings were eligible when index cases and at least one affected sister were diagnosed with infiltrating mammary or ductal @entity420 , with no @entity5345 /2 mutation. In addition, unrelated controls and unaffected sisters were recruited. The enrolment of @entity1 , their relatives and their controls, the collection of the clinical, epidemiological, familial and biological data were centralized by a coordinating center. RESULTS: Inclusion of @entity1 started in February 2007 and ended in December 2013. A total of 1721 index cases, 826 affected sisters, 599 unaffected sisters and 1419 controls were included. 98  % of @entity1 completed the epidemiological questionnaire, 97  % provided a blood sample, and 76  % were able to provide mammograms. Index cases were on average 59  years old at inclusion, were born in 1950, and were 49.7  years of age at @entity0 . The mean age at diagnosis of affected sisters was slightly higher (51.4  years). The representativeness of the control group was verified. CONCLUSIONS: The size of the study, the availability of biological specimens and the clinical data collection together with the detailed and complete epidemiological questionnaire make this a unique national resource for investigation of the missing heritability of @entity0 , by taking into account environmental and life style factors and stratifying data on endophenotypes to decrease genetic heterogeneity.

GENESIS: a French national resource to study the missing heritability of XXXX .

@entity1 :: ('9606', 'Species') :: ['participants', 'women', 'patients'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer diagnosis', 'breast cancer', 'familial breast cancer'] @entity5345 :: ('672', 'Gene') :: ['BRCA1'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity2674 :: ('675', 'Gene') :: ['BRCA2'] @entity420 :: ('MESH:D000230', 'Disease') :: ['adenocarcinoma']
@entity0 :: (MESH:D001943,Disease) :: ['breast cancer']
