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Consanguinity and increased risk for schizophrenia in Egypt.

ABSTRACT: 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 significantly 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.

SUBMITTER: Mansour H

PROVIDER: S-EPMC2900407 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Consanguinity and increased risk for schizophrenia in Egypt.

Mansour Hader H Fathi Warda W Klei Lambertus L Wood Joel J Chowdari Kodavali K Watson Annie A Eissa Ahmed A Elassy Mai M Ali Ibtihal I Salah Hala H Yassin Amal A Tobar Salwa S El-Boraie Hala H Gaafar Hanan H Ibrahim Nahed E NE Kandil Kareem K El-Bahaei Wafaa W El-Boraie Osama O Alatrouny Mohamed M El-Chennawi Farha F Devlin Bernie B Nimgaonkar Vishwajit L VL

Schizophrenia research 20100701 1-3

<h4>Background</h4>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.<h4>Methods</h4>A case-control study was conducted at Mansoura University Hospital, Mansoura, Egypt (SZ, n=75; con ...[more]

PMID: 20435442

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Project description:Prior work in late-onset Alzheimer's disease (LOAD) has resulted in discrepant findings as to whether recent consanguinity and outbred autozygosity are associated with LOAD risk. In the current study, we tested the association between consanguinity and outbred autozygosity with LOAD in the largest such analysis to date, in which 20 LOAD GWAS datasets were retrieved through public databases. Our analyses were restricted to eight distinct ethnic groups: African-Caribbean, Ashkenazi-Jewish European, European-Caribbean, French-Canadian, Finnish European, North-Western European, South-Eastern European, and Yoruba African for a total of 21,492 unrelated subjects (11,196 LOAD and 10,296 controls). Recent consanguinity determination was performed using FSuite v1.0.3, according to subjects' ancestral background. The level of autozygosity in the outbred population was assessed by calculating inbreeding estimates based on the proportion (FROH) and the number (NROH) of runs of homozygosity (ROHs). We analyzed all eight ethnic groups using a fixed-effect meta-analysis, which showed a significant association of recent consanguinity with LOAD (N = 21,481; OR = 1.262, P = 3.6 × 10-4), independently of APOE ∗4 (N = 21,468, OR = 1.237, P = 0.002), and years of education (N = 9,257; OR = 1.274, P = 0.020). Autozygosity in the outbred population was also associated with an increased risk of LOAD, both for F ROH (N = 20,237; OR = 1.204, P = 0.030) and N ROH metrics (N = 20,237; OR = 1.019, P = 0.006), independently of APOE ∗4 [(F ROH, N = 20,225; OR = 1.222, P = 0.029) (N ROH, N = 20,225; OR = 1.019, P = 0.007)]. By leveraging the Alzheimer's Disease Sequencing Project (ADSP) whole-exome sequencing (WES) data, we determined that LOAD subjects do not show an enrichment of rare, risk-enhancing minor homozygote variants compared to the control population. A two-stage recessive GWAS using ADSP data from 201 consanguineous subjects in the discovery phase followed by validation in 10,469 subjects led to the identification of RPH3AL p.A303V (rs117190076) as a rare minor homozygote variant increasing the risk of LOAD [discovery: Genotype Relative Risk (GRR) = 46, P = 2.16 × 10-6; validation: GRR = 1.9, P = 8.0 × 10-4]. These results confirm that recent consanguinity and autozygosity in the outbred population increase risk for LOAD. Subsequent work, with increased samples sizes of consanguineous subjects, should accelerate the discovery of non-additive genetic effects in LOAD.

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Consanguinity and increased risk for schizophrenia in Egypt.

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Consanguinity and increased risk for schizophrenia in Egypt.

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