Familial risks for common diseases: Etiologic clues and guidance to gene identification

Familial clustering of a disease is a direct indicator of a possible heritable cause, provided that environmental sharing can be excluded. If the familial clustering is lacking, the likelihood of a heritable influence is also small. In the era of genome scans, the consideration of data on heritability should be important in the assessment of the likely success of the genome scan. The availability of a Multigeneration Register in Sweden provides a reliable access to families throughout the last century. This Register has been extensively used to study a number of different diseases through linkage to the Hospital Discharge Register. In the present article we review the obtained and some unpublished results for nine main disease classes. For each of these, familial risks are given for four disease subtypes. As measures of familial clustering we use risks between siblings, twins and spouses. Disease correlation between spouses suggests environmental sharing and a higher correlation between siblings and particularly twins shows heritable effects. We will also comment on the established susceptibility genes and the risks conferred by them. The data suggest high heritabilities for chronic obstructive pulmonary disease, asthma, noninfective enteritis and colitis, cerebral palsy and endocrine and metabolic diseases. Among the performed first-generation genome scans on various diseases, the success appears to be related to the a priori heritability estimates. To our knowledge this is a first attempt to summarize familial risks for a large number of diseases using data from a single population on which reasonable uniform diagnostic criteria have been applied. (C) 2008 Elsevier B.V. All rights reserved.