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Quality of CareResearch Programme >
Comorbidity:The aetiological / genetic perspective
Martina C. Cornel, professor of community genetics & public health genomics
Clinical Genetics/EMGO Institute for Health & Care Research
Definition “condition”
Comorbidity: co-existent “conditions”
• Etiology → pathology → manifestation
• Disease → impairment → disability → handicap
WHO, ICIDH, 1980
• Question of patient relates to consequences of disease:
– Feel sad, apathy, headache, cannot go to work, do not manage to perform daily activities, diminished participation, lack of social integration
Definition “condition”
• Comorbidity: co-existent “conditions”:
• Etiology → pathology → manifestation
• Disease → impairment → disability → handicap
WHO, ICIDH, 1980
• Etiology or pathology or disease or impairment?
Epilepsy, dementia, depression?
Etiological diagnosis in genetics
• Down syndrome due to translocation of chromosomes #21 & 14, inherited from mother
• Epicanthus, simian crease, congenital cardiac anomaly
Patterns of malformations in genetics
• Syndromes: Consistent and recognizable patterns of abnormalities for which there will often be a known underlying cause (Down; one cause, several effects)
• Sequences: Consequence of a cascade of events initiated by a single primary factor (Potter: renal agenesis → oligohydramnios → pulmonary hypoplasia and fetal compression → dislocation of hips and talipes).
• Associations: non-random occurrence of abnormalities that cannot be explained on the basis of a sequence or syndrome.
Emery, 2007
Comorbidity: Causes? Consequences?
• Syndromes: One cause, several consequences
• Sequences: Cause, consequence, consequence of consequence
• Associations: recognized pattern in the absence of satisfactory underlying explanation
Recent developments in genetics/genomics
• One gene, one disease (1990-2000)
• Human genome sequenced (2001)
• Genomics research (2001 →)
– Function of genes
– DNA, RNA, proteins, metabolites
– High throughput
– Common disorders
– Multifactorial disorders
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Welcome Trust Case Control
Consortium, Nature 2007
Comorbidity and genetics
Monocausal
• One genotype, several consequences (del 22q11→ cleft palate & schizophrenia & bipolar disorder)
Multifactorial
• Gene variant associated with increased risk of several multifactorial disorders
• Gene function gives information about pathway (pathogenesis)
• Treatment/prevention based on pathway
Comorbidity and genetics
• The challenge in 2009 for common complex disorders:
– Homogeneous subgroups (define phenotype)
– Identify genes involved in multifactorial disorders
– Identify common pathways
– Develop treatment (or prevention) tailored to pathway → both co-existent disorders