Alcohol Alcohol. 2008 Sep-Oct;43(5):505-15. doi: 10.1093/alcalc/agn032. Epub 2008 May 12.

Addictions biology: haplotype-based analysis for 130 candidate genes on a single array.

Hodgkinson CA, Yuan Q, Xu K, Shen PH, Heinz E, Lobos EA, Binder EB, Cubells J, Ehlers CL, Gelernter J, Mann J, Riley B, Roy A, Tabakoff B, Todd RD, Zhou Z, Goldman D.

Source

Laboratory of Neurogenetics, NIAAA, 5625 Fishers Lane, Room 3S32 MSC9412, Rockville, MD 20852-1728, USA. chodg@mail.nih.gov

Abstract

AIMS:

To develop a panel of markers able to extract full haplotype information for candidate genes in alcoholism, other addictions and disorders of mood and anxiety.

METHODS:

A total of 130 genes were haplotype tagged and genotyped in 7 case/control populations and 51 reference populations using Illumina GoldenGate SNP genotyping technology, determining haplotype coverage. We also constructed and determined the efficacy of a panel of 186 ancestry informative markers.

RESULTS:

An average of 1465 loci were genotyped at an average completion rate of 91.3%, with an average call rate of 98.3% and replication rate of 99.7%. Completion and call rates were lowered by the performance of two datasets, highlighting the importance of the DNA quality in high throughput assays. A comparison of haplotypes captured by the Addictions Array tagging SNPs and commercially available whole-genome arrays from Illumina and Affymetrix shows comparable performance of the tag SNPs to the best whole-genome array in all populations for which data are available.

CONCLUSIONS:

Arrays of haplotype-tagged candidate genes, such as this addictions-focused array, represent a cost-effective approach to generate high-quality SNP genotyping data useful for the haplotype-based analysis of panels of genes such as these 130 genes of interest to alcohol and addictions researchers. The inclusion of the 186 ancestry informative markers allows for the detection and correction for admixture and further enhances the utility of the array.