Background: Self-reported consanguinity is associated with risk for schizophrenia (SZ) in several inbred populations, but estimates using DNA-based coefficients of inbreeding are unavailable. Further, it is not known whether recessively inherited risk mutations can be identified through homozygosity by descent (HBD) mapping. Methods: We studied self-reported and DNA-based estimates of inbreeding among Egyptian patients with SZ (n = 421, DSM IV criteria) and adult controls without psychosis (n = 301), who were evaluated using semi-structured diagnostic interview schedules and genotyped using the Illumina Infinium Psych-Array. Following quality control checks, coefficients of inbreeding (F) and regions of homozygosity (ROH) were estimated using PLINK software for HBD analysis. Exome sequencing was conducted in selected cases. Results: Inbreeding was associated with schizophrenia based on self-reported consanguinity (chi(2) = 4.506, 1 df, p = 0.034) and DNA-based estimates for inbreeding (F); the latter with a significant F x age interaction (beta = 32.34, p = 0.0047). The association was most notable among patients older than age 40 years. Eleven ROH were over-represented in cases on chromosomes 1, 3, 6,11, and 14; all but one region is novel for schizophrenia risk. Exome sequencing identified six recessively-acting genes in ROH with loss-of-function variants; one of which causes primary hereditary microcephaly. Conclusions: We propose consanguinity as an age-dependent risk factor for SZ in Egypt. HBD mapping is feasible for SZ in adequately powered samples. (C) 2019 Elsevier B.V. All rights reserved.

We have recently found that consanguinity is a risk factor for bipolar I disorder (BP1) and schizophrenia (SZ) in Egypt. Inbreeding has been associated with increased cellular stress and impaired physiological function in plants and animals. Previous studies have reported that telomere length (TL), an index of oxidative stress and cellular senescence is significantly reduced among patients with SZ or mood disorders compared with control individuals. Hence we evaluated TL as a possible mediator of the observed association between consanguinity and BP1/SZ risk. Patients with BP1 (n=108), or SZ (n=60) were compared with screened adult controls in separate experiments. TL was estimated using a quantitative PCR (qPCR) based assay. The inbreeding coefficient/consanguinity rate was estimated in two ways: using 64 DNA polymorphisms (‘DNA-based’ rate); and from family history data (‘self report’). Significant correlation between TL and DNA based inbreeding was not observed overall, though suggestive trends were present among the SZ cases. No significant case–control differences in TL were found after controlling for demographic variables. In conclusion, reduced TL may not explain a significant proportion of observed associations between consanguinity and risk for BP1/SZ.

Background: Consanguinity has been suggested as a risk factor for psychoses in some Middle Eastern countries, but adequate control data are unavailable. Our recent studies in Egypt have shown elevated parental consanguinity rates among patients with bipolar I disorder (BP1), compared with controls. We have now extended our analyses to schizophrenia (SZ) in the same population.Methods: A case-control study was conducted at Mansoura University Hospital, Mansoura, Egypt (SZ, n = 75; controls, n = 126, and their available parents). The prevalence of consanguinity was estimated from family history data ('self report'), followed by DNA analysis using short tandem repeat polymorphisms (STRPs, n = 63) ('DNA-based' rates).Results: Self-reported consanguinity was significantly elevated among the patients (SZ: 46.6%, controls: 19.8%, OR 3.53, 95% CI 1.88, 6.64; p = 0.000058, 1 d.f). These differences were confirmed using DNA-based estimates for coefficients of inbreeding (inbreeding coefficients as means +/- standard error, cases: 0.058 +/- 0.007, controls: 0.022 +/- 0.003).Conclusions: Consanguinity rates are signifcantly elevated among Egyptian SZ patients in the Nile delta region. The associations are similar to those observed with BP1 in our earlier study. If replicated, the substantial risk associated with consanguinity raises public health concerns. They may also pave the way for gene mapping studies. (C) 2010 Elsevier B.V. All rights reserved.

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 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. © 2009 Wiley‐Liss, Inc.