Review of the studies investigating the effect of inbreeding on complex late onset diseases
| Disease | Author/reference | Study design | Reported effect of inbreeding |
|---|---|---|---|
| *These studies are based on self reported consanguinity which in our experience is unreliable as most “inbreeding loops” are found in the third and fourth parental generations and are thus unknown to most people. | |||
| Coronary heart disease | Shami et al. Lancet1991;: | Case–control study, hospital based | Hospital cases had significantly greater inbreeding coefficients than controls (individuals in population from which they were recruited) |
| Puzyrev et al. Arctic Med Res1992;:–42 | Ecological study | Increased risk of myocardial ischaemia among endogamous males | |
| Jaber et al.* Am J Med Genet1997;:–8 | Case–control study (self reported exposure and outcome status) | No difference in self reported prevalence among students with or without consanguineous parents | |
| Rudan et al (present study), 2003 | Cohort study (with parallel ecological study) | Increased risk associated with greater inbreeding coefficient (relative risk of 1.2 per 3% inbreeding) | |
| Cancer | Simpson et al. Am J Obst Gynecol1981;:–36 | Case–control study, population based | Increased risk of breast, endometrial, and ovarian cancer associated with greater inbreeding coefficient in women under 45 years |
| Lebel & Gallagher. Am J Med Genet1989;:–6 | Case–control study, population based | Increased risk associated with greater inbreeding coefficient, (especially for multiple and early onset cancers) | |
| Shami et al. Lancet1991;: | Case–control study, hospital based | Hospital cases had significantly greater inbreeding coefficients than controls (individuals in population from which they were recruited) | |
| Rudan. Hum Biol1999;:–87 | Ecological study | Stepwise increase of 20 year cancer incidence associated with greater inbreeding in five island communities | |
| Denic & Bener.*Br J Cancer2001;:–9 | Case–control study, population based (self reported exposure status) | Decreased risk of breast cancer among women who self reported being offspring from consanguineous unions, no effect on cervical cancer | |
| Rudan et al (present study), 2003 | Cohort study (with parallel ecological study) | Increased risk associated with greater inbreeding coefficient (relative risk of 2 per 3% inbreeding) | |
| Psychiatric disorders | Abaskuliev & Skoblo. Genetika1975;:–8 | Case–control study, population based | Increased frequency of consanguinity among parents of schizophrenia cases |
| Sangstad & Odegard. Clin Genet1986;:–75 | Case–control study, population based | No increase in first cousin matings among parents of psychiatric patients (major changes in diagnostic criteria over time reported by authors as important confounder) | |
| Gindilis et al. Genetika1989;:–43 | Ecological study | Severe schizophrenia 2–3 times more prevalent in inbred communities | |
| Rudan et al. (present study) 2003 | Cohort study (with parallel ecological study) | Increased risk associated with greater inbreeding coefficient (relative risk of 2.5 [depression] and 5 [schizophrenia] per 3% inbreeding) | |
| Alzheimer’s disease | Vezina et al. Genet Epidemiol1999;:–25 | Case–control study, hospital based | 205 necropsy confirmed cases of late onset Alzheimer’s disease significantly more inbred than controls |
| Multiple sclerosis | Roberts et al. J Epidemiol Community Health1979;:–35 | Case–control population based (with parallel ecological study) | Average inbreeding coefficient greater among cases than controls; increased prevalence in genetic isolate population) |
| Roberts et al. J Epidemiol Community Health1983;:–5 | Case–control population based (with parallel ecological study) | Average inbreeding coefficient greater among cases than controls; increased prevalence in genetic isolate population) | |
| Type 2 diabetes | Jaber et al.* Am J Med Genet1997;:–8 | Case–control study (self reported exposure and outcome status) | No difference in self reported prevalence among students with or without consanguineous parents |
| Rudan et al. (present study) 2003 | Cohort study (with parallel ecological study) | No consistent increase in risk or prevalence associated with greater inbreeding coefficient | |
| Gout | Ombra et al. Am J Hum Genet2001;:–29 | Ecological study | Increased prevalence of hyperuricaemia and uric stones in a highly inbred community |
| Rudan et al. (present study) 2003 | Cohort study (with parallel ecological study) | Increased risk associated with greater inbreeding coefficient (relative risk of 2.5 per 3% inbreeding) | |
| Asthma | Jaber et al.* Am J Med Genet1997;:–8 | Case–control study (self reported exposure and outcome status) | No difference in self reported prevalence among students with or without consanguineous parents |
| Rudan et al. (present study) 2003 | Cohort study (with parallel ecological study) | Increased risk associated with greater inbreeding coefficient (relative risk of 1.5 per 3% inbreeding) | |
| Peptic ulcer | Jaber et al.* Am J Med Genet1997;:–8 | Case–control study (self reported exposure and outcome status) | No difference in self reported prevalence among students with or without consanguineous parents |
| Rudan et al. (present study) 2003 | Cohort study (with parallel ecological study) | Increased risk associated with greater inbreeding coefficient (relative risk of 3 per 3% inbreeding) | |