Volume 41 Issue 1, January 2009

Three new studies identify nearly 20 new loci for serum lipid levels using predominantly a prospective cohort study design which also permits extensive and unbiased characterization of environmental exposures. Given the known, strong environmental influences on these traits, investigation of gene-environment interactions should be emphasized in attempts to understand the complete epidemiologic and genetic architecture of these complex traits.

The identification of targets of virally encoded microRNAs is essential to understanding their role in the viral life cycle. A new study reports the successful use of a microarray-based approach to identify a key target of a microRNA encoded by Kaposi's sarcoma–associated herpesvirus, with implications for microRNA target identification in other contexts as well.

Comparing levels of genetic variation between the X chromosome and autosomes can reveal the different demographic histories of males and females of a species. Taking this approach, two new studies report that the effective population sizes of men and women differ, but they disagree as to which sex outnumbered the other.

DNA methylation is an epigenetic mark directing stable, heritable gene silencing through development. A new study uncovers the importance of demethylation of the DNA methyltransferase-1 for maintenance of DNA methylation.

Unnur Styrkarsdottir and Kari Stefansson and colleagues report the results of an expanded genome-wide association study for bone mineral density at the hip or the spine. New SNP associations were identified downstream of the SOST gene on 17q21, and in intron 1 of the MARK3 gene on 14q32.

Gudmar Thorleifsson and colleagues report results of a large-scale genome-wide association and replication study for obesity-related traits. The newly discovered loci are enriched for genes expressed in the central nervous system, and may thus contribute to weight gain by modulating food intake. Similar results are reported in a related study by Joel Hirschhorn and colleagues.

Joel Hirschhorn and colleagues report results of a large-scale genome-wide association and replication study for obesity-related traits. The newly discovered loci are enriched for genes expressed in the central nervous system, and may thus contribute to weight gain by modulating food intake. Similar results are reported in a related study by Gudmar Thorleifsson and colleagues.

Nelson Freimer and colleagues report the first genome-wide association study of a longitudinal birth cohort (the Northern Finland Birth Cohort 1966). The results include new associations for nine quantitative metabolic traits.

Leena Peltonen and colleagues report a genome-wide association study of cholesterol and triglyceride levels in 16 population-based cohorts across Europe. Six new loci were identified, and overall a genetic risk score improves the screening of high risk groups for dyslipidemia.

Sekar Kathiresan et al. report genome-wide association studies for polygenic dyslipidemia. From a meta-analysis of seven genome-wide association studies and follow-up in five replication studies, they identify 11 new genetic associations for LDL cholesterol, HDL cholesterol and triglycerides.

David Reich and colleagues report evidence for accelerated genetic drift on the X chromosome, on the basis of population genetic analyses comparing patterns of genetic variation on the X chromosome and the autosomes in West African, North European and East Asian datasets.

Alexandra-Chloé Villani and colleagues have identified SNPs located on chromosome 1q44 downstream of the NLRP3 gene that are associated with increased risk of Crohn's disease.

Gonçalo Abecasis and colleagues report associations with fasting plasma glucose levels in a collection of ten genome–wide association scans from the MAGIC consortium. They find variants in the gene encoding melatonin receptor 1B that are associated with fasting glucose levels and, in a meta-analysis of 13 case-control studies, also show association with increased risk of type 2 diabetes.

Leif Groop and colleagues report that, in prospective studies, a variant in the gene encoding melantonin receptor 1B influences future risk of type 2 diabetes. Insulin release from pancreatic beta cells in response to glucose was inhibited by melatonin.

Philippe Froguel and colleagues report an association of variants near the gene encoding melatonin receptor 2 with fasting glucose levels and risk of type 2 diabetes. The association suggests a possible link between circadian rhythm and glucose homeostasis.

Stephen Robertson and colleagues report that germline mutations in WTX cause an X-linked sclerosing bone dysplasia marked by increased bone density and craniofacial malformations in females and lethality in males. In contrast with previous reports showing frequent somatic inactivation of WTX in Wilms tumor, individuals with germline WTX mutations are not predisposed to cancer.

Klaus Schwarz and colleagues report mutations in the gene encoding mitochondrial adenylate kinase 2 in reticular dysgenesis, the most severe form of inborn combined immunodeficiency, characterized by the absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood.

Marina Cavazzana-Calvo and colleagues report mutations in the gene encoding mitochondrial adenylate kinase 2 in reticular dysgenesis, the most severe form of inborn combined immunodeficiency, characterized by the absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood.

Marjolijn Ligtenberg and Suet Leung and colleagues report the identification of germline deletions in TACSTD1, a gene directly upstream of MSH2, in families with Lynch syndrome. The deletions result in transcriptional read-through of TACSTD1 into MSH2, and methylation and silencing of the MSH2 allele.

Mikka Vikkula and colleagues report somatic mutations in the gene encoding the receptor tyrosine kinase TIE2 in inherited and common sporadic venous malformations. These mutations alter localization of the receptor and its response to ligand.

En Li and Taiping Chen and colleagues report that lysine specific demethylase 1 (LSD1, also known as AOF2) demethylates and stabilizes DNA methyltransferase 1 (Dnmt1), and that deletion of Aof2 in embryonic stem cells induces progressive loss of DNA methylation.

Donald Ganem and colleagues report a microarray-based approach to identify microRNA targets. They identify BCLAF1 as a target of miR-K5, a microRNA encoded by the Kaposi's sarcoma–associated herpesvirus.