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Stacy Steinberg, Hreinn Stefansson, Thorlakur Jonsson and colleagues found that rare variants predicted to alter the function of ABCA7 are associated with risk of Alzheimer's disease. The association was found in Iceland and replicated in northern Europe and the United States.

Analysis of whole-genome sequence data of Icelandic individuals has revealed a rare nonsense mutation within the LGR4 gene that is strongly associated with, among other things, low bone mineral density, late onset of menarche, and increased risk of biliary tract cancer.

Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.

Renal cell carcinoma (RCC) accounts for 80–90% of all kidney cancers, but to date, only five genome-wide significant RCC risk loci have been identified. Here, Gudmundsson et al.identify a new RCC susceptibility locus and provide insight into the genetic basis of the disease.

Basal cell carcinoma is a common cancer among people of European ancestry, with associated high economic costs to monitor and treat. Here Stacey et al.conduct a genome-wide association study on Icelandic and other European populations, identifying four novel loci associated with cancer susceptibility.

Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with bone mineral density (BMD) and risk of fracture. Thirty-two new loci are found to be associated with BMD, and 6 loci confer higher risk for low-trauma bone fracture.

Non-medullary thyroid cancers include papillary and follicular subtypes, and are the most common type of thyroid cancer. Here, the authors extend previous work by performing a large genome-wide association study and find five novel loci associated with this disease.

Kari Stefansson and colleagues report the whole-genome sequencing of 2,636 individuals from Iceland to a median of 20× coverage, providing a valuable genomic resource for this population isolate. They characterize patterns of genetic variation and population structure and demonstrate the usefulness of this resource for genetic discovery for several disease phenotypes.

Simon Stacey, Kari Stefansson and colleagues show that a germline variant in the TP53 polyadenylation signal is associated with increased risk of basal cell carcinoma and other solid tumors.

Using a combination of whole-genome sequencing, haplotype sharing and the genealogies of the Icelandic population, Thorunn Rafnar, Kari Stefansson and colleagues identified a rare coding mutation in the gene of a BRCA1-interacting factor, BRIP1, that confers a high relative risk of ovarian cancer.

Julius Gudmundsson and colleagues report a genome-wide association study for circulating levels of thyroid-stimulating hormone in 27,758 individuals not known to have thyroid cancer. They follow with thyroid cancer association analyses and identify common variants at three loci newly associated with susceptibility to thyroid cancer.

Unnur Thorsteinsdottir, Kari Stefansson and colleagues identify low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes. The newly discovered variants include an intronic variant associated with altered expression of CCND2, two independent missense variants in PAM and a rare frameshift variant in PDX1.

Julius Gudmundsson, Kari Stefansson and colleagues identify a low-frequency variant at 8q24 strongly associated with prostate cancer risk. They also confirm association of a recently reported risk variant in HOXB13 in samples from multiple European populations.

Kari Stefansson, Unnur Styrkarsdottir and colleagues identify rare genotypes in COMP and CHADL associated with high risk of total hip replacement due to osteoarthritis. The high odds ratios associated with these rare risk genotypes suggest that they may represent Mendelian forms of osteoarthritis.

Hannes Helgason, Kari Stefansson and colleagues report an association study of gastric cancer susceptibility based on whole-genome sequencing in the Icelandic population. They find that loss-of-function variants in ATM confer risk of gastric cancer.