The task of identifying genetic determinants for complex, multi genetic diseases is hampered by small studies, publication and reporting biases, and lack of common standards worldwide. The authors propose the creation of a network of networks that include groups of investigators collecting data for human genome epidemiology research. Twenty-three networks of investigators addressing speciﬁc diseases or research topics and representing several hundreds of teams have already joined this initiative. For each ﬁeld, the authors are currently creating a core registry of teams already participating in the respective network. A wider international registry will include all other teams also working in the same ﬁeld. Independent investigators are invited to join the registries and existing networks and to join forces in creating additional ones as needed. The network of networks aims to register these networks, teams, and investigators; be a resource for information about or connections to the many networks; offer methodological support; promote sound design and standardization of analytical practices; generate inclusive overviews of ﬁelds at large; facilitate rapid conﬁrmation of ﬁndings; and avoid duplication of effort.
Selective reporting may generate spurious ﬁndings that fail replication (1). Publication bias and selective reporting are well-recognized problems across all domains of epidemiologic and clinical research (5–7). The editors of leading medical journals recently required up-front registration of clinical trials as a prerequisite for eventual publication in their journals (8). However, study registration is difﬁcult to implement in genetic epidemiology: molecular studies often can be carried out rapidly by using established specimen and data collections, and investigators are reluctant to publicly register their hypotheses in advance of publication. An alternative to study registration is to create inclusive registries of investigators and information about sample and/or data collections in different ﬁelds. Whereas individual investigators continue to pursue their chosen lines of research, networks permit broad, consistent, and transparent assessment and replication of novel ﬁndings obtained in individual studies (9). These networks can also facilitate prompt publication—with due credit—of ‘‘negative’’ results and explore reasons for conﬂicting ﬁndings. Finally, the quality and credibility of research can be enhanced by standardization of clinical, laboratory, and statistical methods used by investigators working on the same research questions. Several registries and networks addressing speciﬁc diseases or research questions are already ongoing (9). It is important to share with the international research community at large the expertise and experiences in creating these networks and to provide a comprehensive registry including information on the existing networks. A network of networks is needed to perform this function across diseases and genes. Doing so is critical, because some biologic pathways can affect the risk of many different diseases, and genetic effects also impact multiple pathways and diseases. Moreover, many issues affecting large-scale collaborations such as publication policies, informed consent, biospecimen processing and management, and creation of informatics infrastructures are common to networks across disciplines. The network of networks should offer methodological support, promote sound design and standardization of practices, and generate up-to-date overviews of each ﬁeld. This structure will operate without limiting the scientiﬁc independence of each network to maximize efﬁciency and will avoid unhelpful duplication of efforts. The proposed network-of-networks concept arose at a Human Genome Epidemiology Network–sponsored (10, 11) workshop in Cambridge, United Kingdom, in November 2004 that targeted methodological issues pertaining to the quantitative synthesis of genetic epidemiological information from diverse studies. The workshop was attended by several scientists involved in existing networks. Within a short time, we have grown to include 23 networks representing several hundreds of teams and thousands of individual investigators (table 1) and have identiﬁed many additional networks. Most consortia focus on speciﬁc diseases, but others are organized around a common interest in speciﬁc genes or environmental risk factors modulated by genes. We are currently creating and expanding the core registry that lists information on all teams participating in each existing network, as well as wider registries that also list information on all other teams working in the same ﬁeld worldwide. The wider registries are being compiled based on electronic
searches of the published literature in each ﬁeld, but we also want to identify all investigators interested in working in the speciﬁc area. These efforts will generate a comprehensive map of each ﬁeld and would eventually facilitate creation of a credible synopsis of validated associations of genetic variants with complex disease. We encourage investigators worldwide to communicate with the coordinators of each network (refer to table 1 for contact information) to discuss the possibility of mutually beneﬁcial collaboration. We want to be as inclusive as possible. We also invite other existing networks to join in this initiative, and we encourage investigators who want to create networks in other ﬁelds to communicate with us. An October 6–7, 2005, meeting is being planned in Cambridge, United Kingdom, where network representatives will present and share experiences in creating, managing, and maintaining their collaborations. We would also like to have this meeting attended by scientists interested in creating new networks in their ﬁelds. Other future meetings and consensus statements will aim at developing ‘‘best practices’’ for study designs and standardizing statistical methods for analyzing data from international consortia.