Exome Chip
Contact: Natasja van Schoor
Background
The exome consists of the protein-coding genes in a genome. Approximately 1% of the human genome consists of exons, i.e. the DNA that encodes proteins. Mutations in these coding sequences are much more likely to have severe consequences than in the remaining 99%.
Exome array data covers focused protein-altering variants selected from the exonic regions representing multiple ethnicities and complex traits, but do not include coverage outside of coding regions. Researchers can use these data to obtain new insights from previously genotyped cohorts, or run new studies focused on identifying functionally relevant associations. In LASA, Exome Chip genotyping has been performed in the first cohort.
Measurements in LASA
Blood collection
In the LASA C-cycle (1995/96), blood samples were obtained from respondents who participated in the medical interview of LASA. Respondents were allowed to take tea and toast, but no dairy products. In the LASA G-cycle (2008/09), blood was sampled again under the same conditions.
For the isolation of DNA, buffy coats from 1995/96 (LASA C cycle) or full blood samples from 2008/09 (LASA G cycle) were used. When both buffy coats and full blood samples were available for a respondent, the full blood samples were used. DNA was isolated using standard procedures. 1193 respondents gave permission for genotyping. DNA isolation was performed among 1175 respondents. In 2 persons the DNA concentration or quality was too low, resulting in a total n of 1173.
Measurement procedure & variable information
Genotyping has been performed in 2012 in het Erasmus MC, Department of Internal Medicine, Rotterdam, the Netherlands. Samples were genotyped on the Illumina Human Exome BeadChip v1.1. The Illumina HumanExome Beadchip contains over 240 000 exonic variants, selected from multiple sources with exome sequence data. In total this involved 12000 samples from various populations (African, Chinese, European, Hispanics). Calling was performed on a zCall base. The following quality control (QC) steps were performed after running zCall:
– Individuals with a call ratio < 0.95 were removed
– SNP with a call rate < 0.95 were removed
– Samples with a heterozygote ratio > 0.6 were removed.
Availability of data per wave
The ExomeChip genotyping was performed among respondents from the first cohort (N=1173).
Idats, STS (sample tracking sheet) and Plink files (.bed, .bim, .fam before and after QC) are available. Those data can be requested, but also data from for instance a single or several SNPs, a specific gene, chromosome, or range of SNPs.
Numbers per wave
All regions (C+G combined): N=1173
Previous use in LASA
- Marees, A.T., Hammerschlag, A.R., Bastarache, L., De Kluiver, H., Vorspan, F., Van den Brink, W., Smit, D.J., Denys, D., Gamazon, E.R., Stringa, N. (2018). Exploring the role of low-frequency and rare exonic variants in alcohol and tobacco use. Drug and Alcohol Dependence, 188, 94-101.
Date of last update: April 22, 2020 (NS)
