Consanguinity associated with increased risk for bipolar I disorder in Egypt

Abstract

We aimed to contrast rates of consanguinity among patients with bipolar I disorder (BP1) and controls in a population with customary consanguineous marriages (i.e., marriage between related individuals). Consanguinity increases risk for numerous monogenic and polygenic diseases. Whether the risk for BP1 increases with consanguinity has not been investigated systematically. Two independent studies were conducted in Egypt: (1) Case–control study 93 patients with BP1, 90 screened adult control individuals, and available parents. The inbreeding coefficient/consanguinity rate was estimated in two ways: using 64 DNA polymorphisms (“DNA-based” rate); and from family history data (“self report”); (2) Epidemiological survey: total of 1,584 individuals were screened, from whom self-reported consanguinity data were obtained for identified BP1 cases (n=35) and 150 randomly selected, unaffected control individuals. DNA-based consanguinity rates showed significant case–control control differences (P=0.0039). Self-reported consanguinity rates were also elevated among BP1 patients in both samples (Study #1 OR=2.66, 95% confidence intervals, CI: 1.34, 5.29; Study #2: OR=4.64, 95% CI: 2.01, 10.34). In conclusion, two independent, systematic studies indicate increased consanguinity among Egyptian BP1 patients in the Nile delta region. Self-reported estimates of consanguinity are bolstered by DNA-based estimates, and both show significant case–control differences for BP1.

Consanguinity, human evolution, and complex diseases

“…At the same time, homozygosity mapping in autism (88) and a case-control study of bipolar disorder type 1 in consanguineous progeny (89) both implicated the causal expression of rare recessive genes. ROH similarly have been shown to be significantly more common in patients with schizophrenia spectrum disorders, suggesting the involvement of recessive alleles in the etiology of the disorder (90).…”

Consanguinity, endogamy, and genetic disorders in Tunisia

“…A limited number of reports have focused on the inbreeding effect on multifactorial disorders (Jaber et al 1997;Soliman et al 1999;Bener et al 2001;Rudan et al 2003Rudan et al , 2006Hamamy et al 2005;Alzolibani 2009;Mansour et al 2009). These studies have revealed an important role of inbreeding in the etiology of many specific diseases following a multifactorial pattern of inheritance like diabetes mellitus, hypertension, mental disorders, and cancer.…”

Inbreeding is associated with lower 2D: 4D digit ratio

“…Historically, medical concerns about the deleterious effects of more closely inbred marriages have focused on the risk posed by recessive Mendelian traits, with much less attention to complex disorders and continuous traits (Bittles and Black, 2010). Among the few examples of complex traits however is good, casematched DNA-backed, evidence for an elevated risk for some psychiatric disorders among individuals with consanguineous parentage (Mansour et al, 2009(Mansour et al, , 2010. There appear to be some positive health outcomes associated with consanguineous marriages, such as higher fertility (reviewed in Bittles et al, 1991).…”