Targeted sequencing of ABCA7 identifies splicing, stop-gain and intronic risk variants for Alzheimer disease
| Autor: | Jeffery M. Vance, Goldie S. Byrd, Kara L. Hamilton-Nelson, Rosalyn Lang, Margaret A. Pericak-Vance, Brian W. Kunkle, Adam C. Naj, Patrice L. Whitehead, J. R. Gilbert, Eden R. Martin, Liyong Wang, Regina M. Carney, Martin A. Kohli, Jonathan L. Haines, Michael L. Cuccaro, Gary W. Beecham |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Genotype Population Disease Biology Polymorphism Single Nucleotide White People ABCA7 03 medical and health sciences Alzheimer Disease Humans Genetic Predisposition to Disease education Gene Genetic Association Studies Genetics education.field_of_study General Neuroscience Alternative splicing Sequence Analysis DNA Introns Pedigree White (mutation) Black or African American 030104 developmental biology Cohort biology.protein ATP-Binding Cassette Transporters Female Common disease-common variant |
| Zdroj: | Neuroscience letters. 649 |
| ISSN: | 1872-7972 |
| Popis: | Several variants in the gene ABCA7 have been identified as potential causal variants for late-onset Alzheimer’s disease (LOAD). In order to replicate these findings, and search for novel causal variants, we performed targeted sequencing of this gene in cohorts of non-Hispanic White (NHW) and African-American (AA) LOAD cases and controls. We sequenced the gene ABCA7 in 291 NHW LOAD cases and 103 controls. Variants were prioritized for rare, damaging variants and previously reported variants associated with LOAD, and were follow-up genotyped in 4076 NHW and 1157 AA cases and controls. We confirm three previously associated ABCA7 risk variants and extend two of these associations to other populations, an intronic variant in NHW (P = 3.0 × 10−3) (originally reported in a Belgian population), and a splice variant originally associated in the Icelandic population, which was significantly associated in the NHW cohort (P = 1.2 × 10−6) and nominally associated in the AA cohort (P = 0.017). We also identify a 3′-UTR splice variant that segregates in four siblings of one family and is nominally associated with LOAD (P = 0.040). Multiple variants in ABCA7 contribute to LOAD risk. |
| Databáze: | OpenAIRE |
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