Tag Archives: schizophrenia

Can doctors think?

We already discussed here “how doctors think?k” while a new essay in the Lancet now even asks “Can doctors think“?

Disease can be recognised by the doctor and the patient (mumps), by the doctor but not the patient (schizophrenia), by some doctors but not others (social phobia), by doctors in some times but not others (melancholy …), and by doctors in some places but not others (embedded incisor tooth because an ancestor’s ghost is angry).

marvelous, yea, yea.

Common disease + common variant = common misunderstanding?

Three large studies on schizophrenia now all agree that rare structural variants (CNVs) have a causal role in disease causation – probably by affecting large regions at 1q21 and 15q11 that contain all some “neuro”-genes (Harvard, Decode, Seattle). There are two major points that let me wonder if these papers even mark a turning point in our understanding of genetic causes of human diseases that is largely influenced by the Chakravarti hypothesis of common disease and common variants (CDVC). The Seattle paper had the most clever comment on that

We propose an alternative model: that some mutations predisposing to schizophrenia are highly penetrant, individually rare, and of recent origin, even specific to single cases or families.

Continue reading Common disease + common variant = common misunderstanding?

What could have been learned from linkage studies

What makes the difference between genetic linkage and association studies? Simply speaking, for linkage you need to inherit a particular marker allele from your parents where it does not matter if a child in another family inherits another allele (pending it shares it with its affected sibling). With association studies this matters.

As we found with the much relaxed linkage strategy so many minor diverse loci, I assume a rather heterogeneous origin of complex diseases. There is no doubt about the importance of genes, but about the sharing of the same genetic abnormality. An (anonymous) position paper on basic Asthma Research Strategy II in Clin Exp All 2006; 36: 1326 says

The average size of effect on asthma and related traits from common SNPs is small. For instance, seven common SNPs in the IL13 gene jointly accounted for only 0,5% of the variance of total IgE … With a heritability of circa 60% for total IgE this implies that hundreds of genes, each with small effects, may be involved in IgE regulation.

Families presenting with a complex system disease will all have unique patterns how they arrive at the same clinical endpoint. Alpha-delta-gamma asthma, theta-kappa-jota schizophrenia or $%&# diabetes – are they combining lets say 3000 variations in 300 genes of 30 metabolic-signalling pathways to 1 disease of variable onset, severity and prognosis? Yea, yea.