Ethnic-specific association of amylase gene copy number with adiposity traits in a large Middle Eastern biobank

Studies assessing the impact of amylase genes copy number (CN) on adiposity report conflicting findings in different global populations, likely reflecting the impact of ancestral and ethnic-specific environment and lifestyle on selection at the amylase loci. Here, we leverage population size and detailed adiposity measures from a large population biobank to resolve confounding effects and determine the relationship between salivary (AMY1) and pancreatic (AMY2A) amylase genes CN and adiposity in 2935 Qatari individuals who underwent whole-genome sequencing (WGS) as part of the Qatar Genome Programme. We observe a negative association between AMY1 CNs and trunk fat percentage in the Qatari population (P = 7.50 × 10−3) and show that Qataris of Arab descent have significantly lower CN at AMY1 (P = 1.32 × 10−10) as well as less favorable adiposity and metabolic profiles (P Other Information Published in: npj Genomic Medicine License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41525-021-00170-3</p

Patterns and distribution of de novo mutations in multiplex Middle Eastern families

While de novo mutations (DNMs) are key to genetic diversity, they are also responsible for a high number of rare disorders. To date, no study has systematically examined the rate and distribution of DNMs in multiplex families in highly consanguineous populations. Leveraging WGS profiles of 645 individuals in 146 families, we implemented a combinatorial approach using 3 complementary tools for DNM discovery in 353 unique trio combinations. We found a total of 27,168 DNMs (median: 70 single-nucleotide and 6 insertion-deletions per individual). Phasing revealed around 80% of DNMs were paternal in origin. Notably, using whole-genome methylation data of spermatogonial stem cells, these DNMs were significantly more likely to occur at highly methylated CpGs (OR: 2.03; p value = 6.62 × 10−11). We then examined the effects of consanguinity and ethnicity on DNMs, and found that consanguinity does not seem to correlate with DNM rate, and special attention has to be considered while measuring such a correlation. Additionally, we found that Middle-Eastern families with Arab ancestry had fewer DNMs than African families, although not significant (p value = 0.16). Finally, for families with diseased probands, we examined the difference in DNM counts and putative impact across affected and unaffected siblings, but did not find significant differences between disease groups, likely owing to the enrichment for recessive disorders in this part of the world, or the small sample size per clinical condition. This study serves as a reference for DNM discovery in multiplex families from the globally under-represented populations of the Middle-East.Other Information Published in: Journal of Human Genetics License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s10038-022-01054-9</p

Additional file 1 of A loss-of-function AGTR1 variant in a critically-ill infant with renal tubular dysgenesis: case presentation and literature review

Supplementary Material 1

Willingness to participate in genome testing: a survey of public attitudes from Qatar

Genomics has the potential to revolutionize medical approaches to disease prevention, diagnosis, and treatment, but it does not come without challenges. The success of a national population-based genome program, like the Qatar Genome Program (QGP), depends on the willingness of citizens to donate samples and take up genomic testing services. This study explores public attitudes of the Qatari population toward genetic testing and toward participating in the QGP. A representative sample of 837 adult Qataris was surveyed in May 2016. Approximately 71% of respondents surveyed reported that they were willing to participate in the activities of the QGP. Willingness to participate was significantly associated with basic literacy in genetics, a family history of genetic diseases, and previous experience with genetic testing through premarital screening. Respondents cited the desire to know more about their health status as the principle motivation for participating, while lack of time and information were reported as the most important barriers. With QGP plans to ramp up the scale of its national operation toward more integration into clinical care settings, it is critical to understand public attitudes and their determinants. The results demonstrate public support but also identify the need for more education and individual counseling that not only provide information on the process, challenges, and benefits of genomic testing, but that also address concerns about information security.Other Information Published in: Journal of Human Genetics License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s10038-020-0806-y</p

Comparison of Qatari haplotypes in the regions flanking known single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D) or nearby tag SNPs to the relevant haplotypes of European, Asian, African, or Admixed 1000 Genomes populations.

<p>Admixture deconvolution was used to determine if Qatari haplotypes flanking 64 ‘T2D SNPs’ matched the populations where these SNPs were discovered. Haplotypes were inferred for 100 deeply sequenced Qatari genomes (n = 60 Bedouin Q1, n = 20 Persian Q2, n = 20 African Q3), and divided into 2000 SNP (0.5 cM) intervals. For each interval, SupportMix [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156834#pone.0156834.ref012" target="_blank">12</a>] was used to infer the population with the most similar haplotype, using 1000 Genomes Project Phase 1 as a reference (Admixed = ASW, PUR, CLM, MXL; Asian = CHB, CHS, JPT; African = LWK, YRI; European = TSI, IBS, CEU, FIN, GBR). For each interval containing a T2D risk SNP (n = 64, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156834#pone.0156834.s003" target="_blank">S1 Table</a>), the percentage of Qatari haplotypes assigned to European, Asian, African, or Admixed was determined. Shown is a heatmap of the results, where each column represents a SNP, and each row represents a 1000 Genomes group. Scaled from blue (0%) to tan (100%), colors represent the % of haplotypes for the SNP that are most similar to each Qatari population (Q1, Q2, or Q3).</p

Type 2 Diabetes Risk Allele SNPs.

<p>Type 2 Diabetes Risk Allele SNPs.</p

Population risk allele frequencies.

<p>Population risk allele frequencies (RAF) in <b>A.</b> all Qataris, and <b>B.</b> Q1 and Q2 genetic subpopulations combined, compared to European RAF (obtained from Hapmap [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156834#pone.0156834.ref023" target="_blank">23</a>]) for 37 SNPs previously associated with T2D, with the straight line indicating the regression line of best fit of the data.</p