Premium
P1‐170: WHOLE‐EXOME SEQUENCING IN 20,197 INDIVIDUALS IDENTIFIES ULTRA‐RARE SORL1 LOSS‐OF‐FUNCTION VARIANTS IN LATE‐ONSET ALZHEIMER'S DISEASE
Author(s) -
Raghavan Neha S.,
Brickman Adam M.,
Andrews Howard,
Manly Jennifer J.,
Schupf Nicole,
Lantigua Rafael,
Wolock Charles J.,
Kamalakaran Sitharthan,
Petrovski Slave,
Tosto Giuseppe,
Vardarajan Badri N.,
Goldstein David B.,
Mayeux Richard
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.174
Subject(s) - loss function , exome sequencing , disease , exome , genetics , biology , alzheimer's disease , gene , medicine , mutation , phenotype
P1⁄41.1x10; outbred OR1⁄40.896, P1⁄40.046). HBD-GWAS yielded three significant linkage peaks on Chr. 9p24.3 (DOCK8 gene), on Chr. 5q35.1 (STK10 gene) and on 4q34.3 (NEIL3 gene) (Figure 2). Conclusions: Our work highlights the contribution of consanguinity to the genetic architecture of LOAD. Notably, multiple recessive signals of association and linkagewere uncovered and further research in this field is warranted, by increasing the sample size of consanguineous subjects and by carrying out target sequencing of linkage regions. The study of consanguineous populations should accelerate the discovery of non-additive genetic effects in LOAD.