Genome-wide SNP association: identification of susceptibility alleles for osteoarthritis.

The successful identification of genes involved in common human disorders is dependent upon availability of informative sample sets, validated marker panels, a high-throughput scoring technology, and a strategy for combining these resources. We have developed a universal platform based on mass spectrometry (MassARRAY) for analyzing nucleic acids with high precision and accuracy. To fuel this technology we have generated more than 100,000 validated assays for single nucleotide polymorphisms (SNPs) covering virtually all known and predicted human genes, and a large DNA sample bank from more than 50,000 consented diseased (case) and healthy (control) individuals.

Association of the PDCD5 locus with lung cancer risk and prognosis in smokers.

Purpose: Whole-genome scan association analysis was carried out to identify genetic variants predictive of lung cancer risk in smokers and to confirm the identified variants in an independent sample.

Patients And Methods: A case-control study was performed using two pools consisting of DNA from 322 German smoking lung cancer patients and 273 healthy smoking controls, respectively. A replication study was carried out using 254 Italian lung adenocarcinoma (ADCA) patients and 235 healthy controls.

Association between a variation in LRCH1 and knee osteoarthritis: a genome-wide single-nucleotide polymorphism association study using DNA pooling.

Objective: To perform a large-scale association analysis of single-nucleotide polymorphisms (SNPs) in patients with radiographically defined osteoarthritis (OA) of the knee.

Methods: We examined >25,000 SNPs located within approximately 14,000 genes for associations with radiographically defined knee OA, using polymerase chain reaction and MassExtend amplification techniques. Allele frequencies were estimated initially in DNA pools from 335 female patients with knee OA and 335 asymptomatic and radiographically negative female control subjects.

Genetic polymorphisms in DPF3 associated with risk of breast cancer and lymph node metastases.

Background: Several studies have identified rare genetic variations responsible for many cases of familial breast cancer but their contribution to total breast cancer incidence is relatively small. More common genetic variations with low penetrance have been postulated to account for a higher proportion of the population risk of breast cancer.

Methods And Results: In an effort to identify genes that influence non-familial breast cancer risk, we tested over 25,000 single nucleotide polymorphisms (SNPs) located within approximately 14,000 genes in a large-scale case-control study in 254 German women with breast cancer and 268 age-matched women without malignant disease.

Association between a variation in the phosphodiesterase 4D gene and bone mineral density.

Background: Fragility fractures caused by osteoporosis are a major cause of morbidity and mortality in aging populations. Bone mineral density (BMD) is a useful surrogate marker for risk of fracture and is a highly heritable trait. The genetic variants underlying this genetic contribution are largely unknown.