Sib-pairs in multifactorial disorders: the sib-similarity problem

Common disorders are, by definition, the major cause of ill health and death. Most can be modified by avoiding or shielding an environment, as in sunburn and coeliac disease, by replacing some deficient substance, as in diabetes or myxoedema, or by empirical methods of evident effect as in schizophrenia and depressive illness. As expected, all show an increased incidence in relatives and the identification of the more influential loci involved may define unexpected links in the metabolic map: these may be amenable to therapy, or, in autoimmune disorders and asthma, define precipitating factors by sequencing the receptor involved. The major investment in trawling the genotype for influential loci has been by affected sib-pairs with parents (ASPs). Over a hundred major studies have been published with very limited success. No substantial study of normal sib-pairs has been undertaken, making this family of surveys one of the largest undertaken in the absence of controls. Possible reasons for this limited success and the many suggestive false positives are considered.