French-Canadian Population Research Articles

Validation of the Mayo-Portland Adaptability Inventory-4 (MPAI-4) and reference norms in a French-Canadian population with traumatic brain injury receiving rehabilitation

Purpose Validate the factor structure and establish internal consistency reliability of the French-Canadian version of the Mayo-Portland Adaptability Inventory (MPAI-4), using a Canadian sample of adults with traumatic brain injury (TBI) receiving post-acute rehabilitation services. Materials and methods Psychometric analysis of French-Canadian MPAI-4 data from TBI adults (N = 1012) who received rehabilitation interventions and for whom a first French-Canadian MPAI-4 measure was completed between 2016 and 2020. Results Exploratory factor analysis was used to evaluate the factor structure of the French-Canadian MPAI-4. The final and best solution revealed three factors, which accounted for 48.68% of the variance. Using Cronbach’s alpha, all subscales showed good internal consistency (all 0.70 ≤ α ≤ 0.89). Reference norms for the TBI sample are provided, as well as descriptive raw data according to sex, age, TBI severity and rehabilitation setting. Conclusions The French-Canadian MPAI-4 factor structure is validated. The three factors extracted are similar to the three subscales of the original MPAI-4. The questionnaire shows good psychometric properties and represents a suitable tool for TBI adults receiving rehabilitation services in a French-Canadian context. The provided reference norms will also help guide the clinical use of the MPAI-4 in French-Canadian TBI populations. Implications for rehabilitation The MPAI-4 questionnaire measures functional abilities, global outcome and community integration following traumatic brain injury (TBI). The questionnaire can be used in inpatient, outpatient and vocational rehabilitation settings to assess TBI patients’ progress and outcomes, plan interventions and evaluate the effect of rehabilitation. The French-Canadian version of the MPAI-4 is validated and suitable to be used in French-Canadian post-acute TBI rehabilitation settings.

Validity of the Modified Dyspnea Index for the French-Canadian Population.

Multidimensional tools could evaluate the dyspnea of patients with chronic lung disease. The aim was to validate the use of the French-Canadian version of the modified dyspnea index (MDI) among patients with pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). The Spearman test analyzed the convergent validation of the MDI with pulmonary function tests (PFTs), New York Heart Association (NYHA) functional classification, the Modified Borg Scale, the Veterans Specific Activity Questionnaire (VSAQ), physical capacity, physical activity (Godin-Shephard Leisure-Time Physical Activity Questionnaire [GSLTPAQ]), and quality of life (SF-12). The MDI had a low correlation with PFT and physical activity; a moderate with physical capacity; a high with the physical dimension (SF-12). The results support the convergent validation of the MDI French-Canadian version with PAH or ILD.

Cultural Adaptation and Validation of the Movers Scale in a French-Canadian Population

The purpose of this paper is to present the results of a study that draws upon a collaborative research strategy and has two main objectives: 1) Translating and adapting into French the Measure of Victim Empowerment Related to Safety (MOVERS scale) (Goodman et al. Psychology of Violence, 5(4), 355-366, 2015a); 2) Validating the French version of the MOVERS scale in a population of French-Canadian women receiving shelter services. The French-Canadian MOVERS (FCM) was administered to 189 women receiving shelter services in the province of Quebec (Canada). The factorial structure, reliability and validity of the FCM were tested. This paper highlights that the FCM replicates the three dimensions found in the original version (Goodman et al. Psychology of Violence, 5(4), 355-366, 2015a), displays significant correlations with measures of depression, anxiety and stress, self-esteem, perceived social support, satisfaction with life and self-efficacy, and has overall good reliability estimates. The FCM is a valid and reliable scale to assess safety-related empowerment among women receiving shelter services. Furthermore, the scale provides interesting opportunities to shelter workers, which will be discussed in the paper.

The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

BackgroundGaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients.ResultsThe study cohort included 62 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harbored the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (9%). The median age at diagnosis of the 18 patients harboring the p.G85E mutation was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3075 years.ConclusionThe GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.

Clinical phenotype of adult offspring carriers of the p.Pro392Leu mutation within the SQSTM1 gene in Paget's disease of bone

Paget's disease of bone (PDB) is a common chronic bone disorder. In the French-Canadian population, the p.Pro392Leu mutation within the SQSTM1 gene is involved in 46% of familial forms. In New Zealand, the emergence of PDB in offspring inheriting SQSTM1 mutations was reported to be delayed by a decade compared to their parents. We aimed at assessing the clinical phenotype of offspring carriers of this mutation in our French-Canadian cohort. We reviewed research records from adult offspring carriers of this mutation aged <90 years and their affected parents. In parents, we collected data on sex, age at diagnosis, number of affected bones, total serum alkaline phosphatase levels (tALPs) at diagnosis. In offspring, PDB extended phenotype assessment relying on tALPs, bone specific alkaline phosphatase levels (bALPs), procollagen type 1 amino-terminal propeptide (P1NP), whole body bone scan and skull and pelvis radiographs, was performed at inclusion from 1996 to 2009 and updated in 2016 to 2018, if not done during the past 8 years. The results showed that among the 36 offspring with an updated phenotype, four of them developed a clinical phenotype of PDB characterized by monostotic or polyostotic increased bone uptake associated with typical radiographic lesions in the affected sites, representing an incidence of 1.83 per 1000 person-years. Moreover, the age at PDB diagnosis was delayed by at least 10 years in the adult offspring carriers of the p.Pro392Leu mutation versus their affected parents. Our findings support the utility of a regular monitoring of the adult offspring without PDB but carriers of this mutation.

MON-212 Genetic Spectrum Of A Canadian Cohort Of Sporadic Pheochromocytomas And Paragangliomas: Higher Prevalence Of Germline Mutations In PGL And NGS Assay With A Multigene Panel Increases The Mutation Rate

Background: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) (PPGLs) are rare tumors with a high heritability. The prevalence of germline mutations in sporadic PPGLs varies depending of series. Objective: To determine the prevalence and spectrum of germline mutations in our cohort of patients with apparently sporadic PPGLs. Method: We retrospectively reviewed the charts of patients with sporadic pathology-confirmed PPGLs who underwent genetic testing after genetic counselling at our Quaternary center from 2005–2019. Genetic analysis included sequential gene sequencing by Sanger method from 2005–2014 (n = 89) and a multigene sequencing by NGS with a panel (14 susceptibility genes for PPGLs) from 2015–2019 (n = 34). Some patients underwent both (n = 12). Results: Among 230 patients that were treated for PPGLs from 2005- 2019, 135 patients underwent genetic testing (77 females; 58 males and 77.8% French Canadians). There were 60 PGLs (29 head and neck, 21 abdominal and 10 thoracic) and 75 PHEOs, 4 being bilateral. The prevalence of pathogenic germline mutations was 27.4% (37/135). Patients carrying a germline mutation were younger than patients with no mutations (40.7 yo (20 - 67) vs. 49.6 yo (11 - 80)) and had a higher prevalence of metastatic tumors (26.6% vs. 20.4%). The prevalence of germline mutations was 43.3% (26/60) in PGLs and 14.7% (11/75) in PHEOs. In the 26 mutated PGLs, there were 13 SDHC (50.0%), 6 SDHB (23.1%), 4 SDHD (15.4%), 2 SDHA (7.7%) and 1 FH (3.8%) mutations. The recurrent pathogenic SDHC c.397C>T (p.Arg133*) mutation was found in 12 out of the 13 SDHC mutations reflecting the presence of a funder effect in the French Canadian population. In the 11 mutated PHEOs, there were 3 MAX (27.3%), 3 VHL (27.3%), 2 RET (18.2%), 1 SDHB (9.1%), 1 NF1 (9.1%), 1 FH (9.1%) mutations.From 2015- 2019, we proposed NGS assay with the multigene panel to 12 patients (9 PHEOS and 3 PGLs) for whom the initial genetic test was negative. Novel germline mutations were found in 4 (33.3%) of these patients, representing 10.8% (4/37) of the mutation-carriers. Mutations were found in 2/9 PHEOs; a 28 yo female with bilateral PHEOs (MAX (deletion exon 1 and 2)) and a 33 yo male with malignant PHEO (MAX (c.3G>A)), and in 2/3 PGLs; a 31 yo woman with metastatic abdominal PGL (SDHA (c.985C>T) and a 59 yo woman with a thoracic PGL (SDHA (c.1432_1432 + 1del).Variants of uncertain significance (VUS) were identified in 7/60 PGLs (11.6%) and 5/75 PHEOs (6.7%) but the significance of these variants remains to be determined. Conclusion: In our cohort, the prevalence of germline mutations was of 44.3% in apparently sporadic PGLs and 14.7% in PHEOs. Genetic re-evaluation overtime using multigene sequencing by NGS assay in a subgroup of patients led to an increase of mutation rate in PHEOs and PGLs with the identification of germline MAX and SDHA mutations.

The incidence and carrier frequency of Tay-Sachs disease in the French-Canadian population of Quebec based on retrospective data from 24 years, 1992-2015.

Tay-Sachs disease (TSD) is a hereditary neurodegenerative condition inherited through an autosomal recessive pattern. The incidence and carrier frequency of infantile TSD were found to be increased among French Canadians in specific areas of the province of Quebec or calculated from New England populations with French-Canadian heritage. No accurate infantile TSD carrier frequency for the whole French-Canadian population in Quebec has been published. In this study, we estimate the incidence and carrier frequency of infantile TSD in the Quebec French-Canadian population. The number of TSD cases was ascertained during the 1992-2015 period, as well as the number of births to mothers whose language of use is French. Seven cases of TSD have been diagnosed in Quebec during the period of ascertainment. This corresponds to an incidence of 1/218,144, which in turn corresponds to a carrier frequency of 1/234. In the same 24-year period, there are two French-Canadian couples who had a fetus prenatally diagnosed with TSD. If these cases are included, the incidence of TSD in the French-Canadian population of Quebec is 1/169,668 and the carrier frequency 1/206. These findings can be used for genetic counseling and policy decisions regarding carrier screening for TSD in populations of French-Canadian descent.

Founder BRCA1/BRCA2/PALB2 pathogenic variants in French-Canadian breast cancer cases and controls

Inherited germline pathogenic variants are responsible for ~5% of breast cancer globally. Through rapid expansion and isolation since immigration in the early 17th century, French Canadians are a relatively genetically homogenous founder population and therefore represent a unique demographic for genetic contributions to disease. To date, twenty variants in BRCA1, BRCA2, and PALB2 that predispose families to breast and ovarian cancer have been identified as recurring in the French-Canadian founder population. Our objective was to evaluate the clinical efficacy and validity of targeted genetic testing for these variants in Montreal French Canadians. A total of 555 breast cancer cases unselected for family history or age of diagnosis were genotyped, along with 1940 controls without a personal or family history of cancer. A Sequenom genotyping assay identified a pathogenic variant in 0.2% (5 of 1940) of cancer-free controls, and 3.8% (21/555) of breast cancer cases. Almost 10% (12/113) of early onset cases were heterozygous for founder BRCA1 or BRCA2 pathogenic variant. Of twenty variants tested, only seven were identified in this study. The option of providing this test as population-based screening is discussed.

Development of the French-Canadian Version of the Self-Administered Comorbidities Questionnaire (SCQ) in a hospital population undergoing hip or knee arthroplasty

The Self-Administered Comorbidity Questionnaire (SCQ) is a tool used by hospitalized patients to self-report their comorbidities. It can help to explain the effectiveness of hip or knee arthroplasty, its complications, the length of hospital stay and perioperative resource utilization. HypothesisThe French-Canadian version of the SCQ will be suitable for use in a Canadian hospital population. Objectives(1) translate and evaluate the transcultural validity of the SCQ in a French Canadian population undergoing hip or knee arthroplasty; (2) determine the standard error of measurement (SEM) in the French Canadian version. Materials and MethodsThe translation and transcultural adaptation process consisted of four steps: (1) initial translation; (2) back translation; (3) assessment of questionnaire clarity with patients; (4) assessment of the translation's transcultural validity. The SEM was also calculated. ResultsTwenty participants were recruited for step 3 and 83 participants for step 4. The original English version of the SCQ and the translated French-Canadian version (SCQ-FC) were similar with intra-class correlation coefficients for the intra-language and inter-language agreement between 0.71 and 0.97. The SEM was 1.92. ConclusionThe SCQ-FC is comparable to the original English language version. Using this questionnaire allows us to document the comorbidities present in patients undergoing hip and knee arthroplasty in a French-Canadian population, and the impact of these comorbidities on the patients’ health. Level of evidenceV, Prospective study.

Dental age estimation using Willems method: A cross-sectional study on children in a North Indian city

Background:Numerous methods of age estimation have been proposed. The Demirjian method which was first applied in a French-Canadian population in 1972 is the most frequently used dental age estimation method. However, a constant over estimation using this method has been reported by numerous researchers. The Willems method is a modification of the above and was first applied in a Belgian Caucasian population in 2002. Several studies in the recent years found Willems method to be more accurate than the original Demirjians method.Objectives:The objective of this study was to evaluate the applicability of Willems method for dental age estimation in 6 -15-year-old North Indian children.Methods:The sample for this cross sectional study consisted of 390 OPGs of (215 boys and 175 girls) randomly selected from the patient records of a post graduate training dental college in North India. Exact chronological age of the subjects (in years and months) was calculated. The OPGs were used to score the seven mandibular teeth and dental age was estimated using the tables proposed in Willems method.Results:Significant correlation between the chronological age and dental age estimated using Willems method was observed in both males (r = 0.90) and females (r = 0.87). The mean difference between estimated DA and CA for males was 0.004 ± 1.08 years (P = 0.94). While for females, it was 0.031 ± 1.18 years (P = 0.72). The results showed no statistically significant difference between chronological age and dental age estimated using Willems method in the study population.Conclusion:Willems dental age estimation method without any modification can predict the chronological age of 6-15 year old North Indian children with good accuracy.

Measurement Comparability of Reading in the English and French Canadian Populations: Special Case of the 2011 Progress in International Reading Literacy Study

The purpose of this study is to examine item equivalence and score comparability of the Progress in International Reading Literacy Study (PIRLS) 2011for the Canadian French and English language groups. Two methods of differential item functioning were conducted to examine item equivalence across thirteen test booklets designed to assess reading literacy in early years of schooling. Four bilingual reviewers with expertise in reading literacy conducted independent, linguistic and cultural reviews to identify both the degree of item equivalence and potential sources of differences between language versions of released items. Results indicate that an average of 25% of items per booklet function differently at the item level. Reviews by experts indicate differences between the two language versions on some items flagged as displaying differential item function (DIF). Some of these were identified to have linguistic differences pointing to differential difficulty levels in the two language versions.

Cross-Cultural Adaptation and Reliability of the French-Canadian Version of the European Heart Failure Self-Care Behaviour Scale-9.

The purposes of this methodological study were to adapt the European Heart Failure Self-care Behaviour Scale-9 to the French-Canadian population and to evaluate its reliability. The adaptation process consisted of translation, back-translation, evaluation by an expert committee, and pretesting. Reliability was evaluated with stability criteria (test-retest) and internal consistency. Pretesting led to testing of two response formats: 5-point Likert scale and the frequency scale. Both demonstrated good levels of agreement between the test-retest, although the values were higher with the frequency format. The Cronbach's alpha coefficients ranged from 0.71 to 0.78 (Likert scale) and 0.70 to 0.83 (frequency scale). The French-Canadian version of the EHFScB-9, in both formats, demonstrated good evidence of reliability.

Applicability of Demirjian’s method for age estimation in a sample of Italian children with Down syndrome: A case-control retrospective study

Age estimation is widely applied in several clinical and forensic fields. The radiographic evaluation of dental development is one of the most accepted tools for this purpose. Among the different methods proposed, Demirjian’s method was the most extensively used and tested in the medical literature revealing that the original standards for the French–Canadian population tends to over-estimate the age of different population groups. The aims of this study were to evaluate the applicability of the Demirjian method in a sample of Italian children with Down syndrome (DS) and to compare the data with age and gender matched healthy subjects (non-DS). A retrospective study was performed on 146 orthopantomograms of DS individuals aged 6.3–16 years. The mean chronological age (CA) and the mean dental age (DA) were calculated. Using Cohen’s kappa statistics, the inter- and intra-examiner agreement was reported as good (k = 0.75) and very good (k = 0.86). The differences between CAs and DAs were statistically significant for males and females (Wilcoxon Signed Rank test; p < 0.05). The median overestimation was 0.6 years in males and 0.9 years in females. Demirjian’s method is unsuitable for dental age estimation in DS individuals. The same trend in overestimation was found in the control group. Comparing DS and non-DS subjects, the differences between DAs were not statistically significant for both males and females revealing that the dental development process is similar.

RNF213 Variant Diversity Predisposes Distinct Populations to Dissimilar Cerebrovascular Diseases.

In recent years, the ring finger protein 213 gene (RNF213) has gradually attracted attention, mainly because it has been found that RNF213 c.14429 G>A is associated with moyamoya disease (MMD) in East Asian populations. Recent studies have revealed that RFN213 is not only associated with MMD but is also connected with intracranial major artery stenosis/occlusion (ICASO) and intracranial aneurysm (IA). However, only the relationship between RNF213 c.14429 G>A and ICASO has been confirmed, and whether RNF213 has other mutations related to ICASO remains unclear. RNF213 and IA are currently only confirmed to be correlated in French-Canadian Population and no correlation has been found in the Japanese population. This review summarizes the advances in the associations between RNF213 and different cerebrovascular diseases and highlights that variant diversity of RNF213 may predispose distinct populations to dissimilar cerebrovascular diseases.

Inferring Transmission Histories of Rare Alleles in Population-Scale Genealogies

Learning the transmission history of alleles through a family or population plays an important role in evolutionary, demographic, and medical genetic studies. Most classical models of population genetics have attempted to do so under the assumption that the genealogy of a population is unavailable and that its idiosyncrasies can be described by a small number of parameters describing population size and mate choice dynamics. Large genetic samples have increased sensitivity to such modeling assumptions, and large-scale genealogical datasets become a useful tool to investigate realistic genealogies. However, analyses in such large datasets are often intractable using conventional methods. We present an efficient method to infer transmission paths of rare alleles through population-scale genealogies. Based on backward-time Monte Carlo simulations of genetic inheritance, we use an importance sampling scheme to dramatically speed up convergence. The approach can take advantage of available genotypes of subsets of individuals in the genealogy including haplotype structure as well as information about the mode of inheritance and general prevalence of a mutation or disease in the population. Using a high-quality genealogical dataset of more than three million married individuals in the Quebec founder population, we apply the method to reconstruct the transmission history of chronic atrial and intestinal dysrhythmia (CAID), a rare recessive disease. We identify the most likely early carriers of the mutation and geographically map the expected carrier rate in the present-day French-Canadian population of Quebec.

Cross-Cultural Adaptation of the Cardiff Fertility Knowledge Scale and the Fertility Status Awareness Tool for the French-Canadian Population.

The Cardiff Fertility Knowledge Scale (CFKS) and the Fertility Status Awareness Tool (FertiSTAT) are validated tools allowing the evaluation of fertility knowledge and raising awareness about risk indicators for reduced fertility. Their use by health care professionals practicing in the field of reproductive health might optimize fertility of the Canadian population. However, there currently is no version of these questionnaires for the French-Canadian population. The objective of this study was to translate and culturally adapt the CFKS and FertiSTAT to the French-Canadian population. The translation and adaptation of the questionnaires was completed following a four-stage approach: (1) forward translation, (2) synthesis, (3) expert committee review, and (4) testing of the prefinal version of the questionnaires. The testing stage was conducted with a sample of 30 women and 10 men. During the translation process, linguistic difficulties were met for some items of both questionnaires but were resolved by consensus of the expert committee. Thirty women and 10 men tested the prefinal version of the CFKS-F and FertiSTAT-F. On a 5-point Likert scale, the global comprehension was 4.8 ± 0.5 and 4.6 ± 0.6, respectively. Based on the comments of the participants, the expert committee made minor modifications in the final version of the questionnaires to clarify the formulation of questions and adapt to one medical term. Tools to assess fertility knowledge and the presence of risk indicators for reduced fertility are now available for health care professionals practicing in the field of reproductive health.

Assessing the relative validity of a new, web-based, self-administered 24 h dietary recall in a French-Canadian population.

To assess the relative validity of a new, web-based, self-administered 24 h dietary recall, the R24W, for assessment of energy and nutrient intakes among French Canadians. Each participant completed a 3d food record (FR) and the R24W on three occasions over a 4-week period. Intakes of energy and of twenty-four selected nutrients assessed by both methods were compared. Québec City metropolitan area. Fifty-seven women and fifty men (mean (sd) age: 47·2 (13·3) years). Equivalent proportions of under-reporters were found with the R24W (15·0%) and the FR (23·4%). Mean (sd) energy intake from the R24W was 7·2% higher than that from the FR (10 857 (3184) kJ/d (2595 (761) kcal/d) v. 10 075 (2971) kJ/d (2408 (710) kcal/d); P<0·01). Significant differences in mean nutrient intakes between the R24W and the FR ranged from -54·8% (i.e. lower value with R24W) for niacin to +40·0% (i.e. higher value with R24W) for alcohol. Sex- and energy-adjusted deattenuated correlations between the two methods were significant for all nutrients except Zn (range: 0·35-0·72; P<0·01). Cross-classification demonstrated that 40·0% of participants were classified in the same quartile with both methods, while 40·0% were classified in the adjacent quartile and only 3·6% were grossly misclassified (1st v. 4th quartile). Analysis of Bland-Altman plots revealed proportional bias between the two assessment methods for 8/24 nutrients. These data suggest that the R24W presents an acceptable relative validity as compared with the FR for estimating usual dietary intakes in a cohort of French Canadians.

Social support for healthy eating: development and validation of a questionnaire for the French-Canadian population.

The present study aimed to develop and validate a questionnaire assessing social support for healthy eating in a French-Canadian population. A twenty-one-item questionnaire was developed. For each item, participants were asked to rate the frequency, in the past month, with which the actions described had been done by family and friends in two different environments: (i) at home and (ii) outside of home. The content was evaluated by an expert panel. A validation study sample was recruited and completed the questionnaire twice. Exploratory factor analysis was performed on items to assess the number of subscales. Internal consistency reliability was assessed using Cronbach's ɑ. Test-retest reliability was evaluated with intraclass correlations between scores of the two completions. Online survey. Men and women from the Québec City area (n 150). The content validity assessment led to a few changes, resulting in a twenty-two-item questionnaire. Exploratory factor analysis revealed a two-factor structure for both environments, resulting in four subscales: supportive actions at home; non-supportive actions at home; supportive actions outside of home; and non-supportive actions outside of home. Two items were removed from the questionnaire due to low loadings. The four subscales were found to be reliable (Cronbach's ɑ=0·82-0·94; test-retest intraclass correlation=0·51-0·70). The Social Support for Healthy Eating Questionnaire was developed for a French-Canadian population and demonstrated good psychometric properties. This questionnaire will be useful to explore the role of social support and its interactions with other factors in predicting eating behaviours.

Familial hypercholesterolemia: experience from the French-Canadian population.

There has recently been renewed interest in the study of the various facets of familial hypercholesterolemia, a severe monogenic disease associated with elevated LDL-cholesterol and premature cardiovascular disease (CVD). In the present review, novel data presenting the frequency of familial hypercholesterolemia as well as factors modulating the cardiovascular risk in familial hypercholesterolemia will be discussed. Recent studies have showed that familial hypercholesterolemia is much more prevalent than initially thought. Classically, it was estimated that familial hypercholesterolemia affected one in 500 people worldwide, but a recent large-scale meta-analysis has shown a prevalence closer to one in 250. In the French-Canadian population, this disease is even more frequent reaching one in 81 in certain regions of the Province of Quebec. Several novel studies in the French-Canadian population have shown that the clinical outcomes in familial hypercholesterolemia seem to be greatly influenced by risk factors other than LDL-cholesterol. Also, scores to predict CVD in familial hypercholesterolemia have been recently proposed. Familial hypercholesterolemia is more frequent than initially thought and the phenotype of this disease can be variable. Indeed, both clinical and genetic variables can modulate the CVD risk in this population.

Genome-wide association analysis identifies new candidate risk loci for familial intracranial aneurysm in the French-Canadian population

Intracranial Aneurysm (IA) is a common disease with a worldwide prevalence of 1–3%. In the French-Canadian (FC) population, where there is an important founder effect, the incidence of IA is higher and is frequently seen in families. In this study, we genotyped a cohort of 257 mostly familial FC IA patients and 1,992 FC controls using the Illumina NeuroX SNP-chip. The most strongly associated loci were tested in 34 Inuit IA families and in 32 FC IA patients and 106 FC controls that had been exome sequenced (WES). After imputation, one locus at 3p14.2 (FHIT, rs1554600, p = 4.66 × 10–9) reached a genome-wide significant level of association and a subsequent validation in Nunavik Inuit cohort further confirmed the significance of the FHIT variant association (rs780365, FBAT-O, p = 0.002839). Additionally, among the other promising loci (p < 5 × 10−6), the one at 3q13.2 (rs78125721, p = 4.77 × 10−7), which encompasses CCDC80, also showed an increased mutation burden in the WES data (CCDC80, SKAT-O, p = 0.0005). In this study, we identified two new potential IA loci in the FC population: FHIT, which is significantly associated with hypertensive IA, and CCDC80, which has potential genetic and functional relevance to IA pathogenesis, providing evidence on the additional risk loci for familial IA. We also replicated the previous IA GWAS risk locus 18q11.2, and suggested a potential locus at 8p23.1 that warrants further study.