Dora Stadler

Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar

Exome sequencing of families of related individuals has been highly successful in identifying genetic polymorphisms responsible for Mendelian disorders. Here, we demonstrate the value of the reverse approach, where we use exome sequencing of a sample of unrelated individuals to analyze allele frequencies of known causal mutations for Mendelian diseases. We sequenced the exomes of 100 individuals representing the three major genetic subgroups of the Qatari population (Q1 Bedouin, Q2 Persian‐South Asian, Q3 African) and identified 37 variants in 33 genes with effects on 36 clinically significant Mendelian diseases. These include variants not present in 1000 Genomes and variants at high frequency when compared with 1000 Genomes populations. Several of these Mendelian variants were only segregating in one Qatari subpopulation, where the observed subpopulation specificity trends were confirmed in an independent population of 386 Qataris. Premarital genetic screening in Qatar tests for only four out of the 37, such that this study provides a set of Mendelian disease variants with potential impact on the epidemiological profile of the population that could be incorporated into the testing program if further experimental and clinical characterization confirms high penetrance.

The Qatar genome: a population-specific tool for precision medicine in the Middle East.

Reaching the full potential of precision medicine depends on the quality of personalized genome interpretation. In order to facilitate precision medicine in regions of the Middle East and North Africa (MENA), a population-specific genome for the indigenous Arab population of Qatar (QTRG) was constructed by incorporating allele frequency data from sequencing of 1,161 Qataris, representing 0.4% of the population. A total of 20.9 million single nucleotide polymorphisms (SNPs) and 3.1 million indels were observed in Qatar, including an average of 1.79% novel variants per individual genome. Replacement of the GRCh37 standard reference with QTRG in a best practices genome analysis workflow resulted in an average of 7* deeper coverage depth (an improvement of 23%) and 756,671 fewer variants on average, a reduction of 16% that is attributed to common Qatari alleles being present in QTRG. The benefit for using QTRG varies across ancestries, a factor that should be taken into consideration when selecting an appropriate reference for analysis.

Clinician-educators in emerging graduate medical education systems: description, roles and perceptions

Objectives To describe clinician-educators (CEs) in new graduate medical education (GME) systems and characterize perception of preparedness, roles and rewards, and factors affecting job satisfaction and retention. Methods A cross-sectional survey of all CEs of institutions using competency-based GME and accredited by the Accreditation Council for Graduate Medical Education-International (ACGME-I). Results 274 of 359 eligible participants (76.3%) responded, representing 47 residency programs across 17 specialties. CEs were predominantly married men aged in their 40s, employed at their current institution 9.3 years (±6.4 years). CEs judged themselves competent or expert in teaching skills (91.5%), trainee assessment (82%) and mentoring (75%); less so in curriculum development (44%) and educational research skills (32%). Clinical productivity was perceived by the majority (62%) as the item most valued by their institutions, with little or no perceived value for teaching or educational efforts. Overall, 58.3% were satisfied or very satisfied with their roles, and 77% expected to remain in academic medicine for 5 years. A strong negative correlation was found between being a program or associate program director and likelihood of staying in academic medicine (aOR 0.42; 0.22 to 0.80). Conclusions In the GME systems studied, CEs, regardless of country or programme, report working in environments that value clinical productivity over educational efforts. CEs feel competent and prepared for many aspects of their roles, have positive attitudes towards teaching, and report overall job satisfaction, with most likely to remain in academic medicine. As medical training advances internationally, the impact on and by CEs requires ongoing attention.

Type 2 Diabetes Risk Allele Loci in the Qatari Population.

Background The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians. Methods All subjects were ≥3 generation Qataris. Cases with T2D (n = 1,124) and controls (n = 590) were randomly recruited and assigned to the 3 known Qatari genetic subpopulations [Bedouin (Q1), Persian/South Asian (Q2) and African (Q3)]. Subjects underwent genotyping for 37 single nucleotide polymorphisms (SNPs) in 29 genes known to be associated with T2D in Europeans and/or Asian populations, and an additional 27 tag SNPs related to these susceptibility loci. Pre-study power analysis suggested that with the known incidence of T2D in adult Qataris (22%), the study population size would be sufficient to detect significant differences if the SNPs were risk factors among Qataris, assuming that the odds ratio (OR) for T2D SNPs in Qatari’s is greater than or equal to the SNP with highest known OR in other populations. Results Haplotype analysis demonstrated that Qatari haplotypes in the region of known T2D risk alleles in Q1 and Q2 genetic subpopulations were similar to European haplotypes. After Benjamini-Hochberg adjustment for multiple testing, only two SNPs (rs7903146 and rs4506565), both associated with transcription factor 7-like 2 (TCF7L2), achieved statistical significance in the whole study population. When T2D subjects and control subjects were assigned to the known 3 Qatari subpopulations, and analyzed individually and with the Q1 and Q2 genetic subpopulations combined, one of these SNPs (rs4506565) was also significant in the admixed group. No other SNPs associated with T2D in all Qataris or individual genetic subpopulations. Conclusions With the caveats of the power analysis, the European/Asian T2D SNPs do not contribute significantly to the high prevalence of T2D in the Qatari population, suggesting that the genetic risks for T2D are likely different in Qataris compared to Europeans and Asians.

Gender and international clinician educators

Objectives To describe gender differences of international clinician educators (CEs) and leaders, and CEs’ perceptions by gender of preparation, roles, rewards and factors affecting job satisfaction and retention in emerging international competency-based residency programmes. Methods Cross-sectional surveys of CEs and leadership were conductedJune 2013–June 2014 at institutions that had adopted competency-based graduate medical education and were accredited by the Accreditation Council for Graduate Medical Education-International. Results 274 (76.3%) of 359 eligible participants responded; 69 (25.2%) were female. Two (18%) of 11 chief executive officers and 1 (9%) of 11 chief medical officers were women. Female CEs were younger, more likely to be single and childless. They were less likely to hold academic appointments, despite no gender differences in length of time at current institution or in current position. A greater proportion of female CEs felt they were ‘never’ rewarded by academic promotion. Satisfaction rates were similar between the genders. Single female CEs were five times as likely to report being ‘extremely likely’ to stay in the country. Female CEs with children <21 were less likely to report high likelihood of staying in academia. Marital status and children were not associated with outcomes for male CEs. Conclusions In the international academic medicine programmes studied, there were fewer female CEs in the pipeline and they perceived a gender gap in appointment and advancement. Stakeholders at international programmes need to develop contextualised strategies to expand entry and decrease attrition of women into CE tracks, and promote gender equity.

Exome sequencing-based identification of novel type 2 diabetes risk allele loci in the Qatari population

Background Type 2 diabetes (T2D) susceptibility is influenced by genetic and lifestyle factors. To date, the majority of genetic studies of T2D have been in populations of European and Asian descent. The focus of this study is on genetic variations underlying T2D in Qataris, a population with one of the highest incidences of T2D worldwide. Results Illumina HiSeq exome sequencing was performed on 864 Qatari subjects (574 T2D cases, 290 controls). Sequence kernel association test (SKAT) gene-based analysis identified an association for low frequency potentially deleterious variants in 6 genes. However, these findings were not replicated by SKAT analysis in an independent cohort of 12,699 exomes, primarly due to the absence of low frequency potentially deleterious variants in 5 of the 6 genes. Interestingly one of the genes identified, catenin beta 1 (CTNNB1, β-catenin), is the key effector of the Wnt pathway and interacts with the nuclear receptor transcription factor 7-like 2 (TCF7L2), variants which are the most strongly associated with risk of developing T2D worldwide. Single variant analysis did not identify any associated variants, suggesting the SKAT association signal was not driven by individual variants. None of the 6 associated genes were among 634 previously described T2D genes. Conclusions The observation that genes not previously linked to T2D in prior studies of European and Asian populations are associated with T2D in Qatar provides new insights into the complexity of T2D pathogenesis and emphasizes the importance of understudied populations when assessing genetic variation in the pathogenesis of common disorders.

Characterization and Perceptions of Surgical Clinician Educators: An International Survey

OBJECTIVE Surgeons worldwide face unique time and practice pressures differentiating them from other types of physicians, specifically as clinician educators (CEs). The purpose of this study is to identify and describe academic surgical clinician educators (SCEs) in international graduate medical education systems, characterize their perceptions of roles, preparedness, and factors affecting job satisfaction and retention, as compared to nonsurgical international CEs. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional survey of CEs was conducted June 2013-June 2014 at academic medical centers in Singapore, Qatar, and the United Arab Emirates that adopted competency-based graduate medical education and received accreditation by the Accreditation Council for Graduate Medical Education-International. RESULTS Two hundred seventy-six (76.3%) of 359 eligible physicians responded; 64 (23.2%) were SCEs. SCEs were predominantly male (80%), less than 50 years of age (83%), with 64% having been in their current position less than 5 years. Overall, SCEs were significantly less confident, as compared to nonsurgical CEs, in aspects of educational programs, including curriculum development, assessment, and mentorship. SCEs spent significantly more time engaged in patient care activities, as compared to nonsurgeon colleagues. There were no significant differences between SCEs and nonsurgical CEs in terms of work-life balance and satisfaction with responsibilities, position, or potential promotion, with most SCEs intending to stay in academic medicine. CONCLUSIONS Academic SCEs working in the international programs reported overall job satisfaction with a desire to remain in academic medicine. However, SCEs have several faculty development needs. International surgical training programs can develop and expand offerings in teaching and education to improve skills and maintain SCE satisfaction and retention, necessary to successfully train the next generation of surgeons.

Twelve tips to promote gender equity in international academic medicine

Abstract Gender inequity in academic medicine remains an important issue worldwide, with more female faculty entering academic medicine internationally. Some academic institutions have initiated programs and created policies to promote gender equity, but disparities remain in faculty numbers, promotions rates, research productivity and access to funding and resources. We offer 12 tips for best practices in the broad domains of faculty recruitment, retention and scholarship, promotion and leadership that institutions and individual faculty can adopt to promote gender equity. While the 12 tips form a comprehensive approach, each tip can be implemented individually depending on institutional needs and culture. Each tip includes practical advice for implementation supported by a successful example from the literature.

Correction: Type 2 Diabetes Risk Allele Loci in the Qatari Population

[This corrects the article DOI: 10.1371/journal.pone.0156834.].