Author Correction: Genetics of 35 blood and urine biomarkers in the UK Biobank

Sinnott-Armstrong, Nasa; Tanigawa, Yosuke; Amar, David; Mars, Nina; Benner, Christian; Aguirre, Matthew; Venkataraman, Guhan; Wainberg, Michael; Ollila, Hanna; Kiiskinen, Tuomo; Havulinna, Aki S.; Qian, Junyang; Shcherbina, Anna; FinnGen,; Rodríguez, Fátima; Assimes, Themistocles L.; Agarwala, Vineeta; Tibshirani, Robert; Hastie, Trevor; Ripatti, Samuli; Pritchard, Jonathan K.; Daly, Mark J.; Rivas, Manuel A.

doi:10.1038/s41588-021-00956-2

Cited by 11 publications

(37 citation statements)

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“…We combined the results of the QBB GWAS and a recent large GWAS (GCST90019526) from the UK Biobank by the N Sinnott-Armstrong et al (10). to derive a combined meta-analysis for the suggestively associated loci.…”

Section: Meta-analysismentioning

confidence: 99%

“…The rst QBB dataset release (N = 6,218 individuals) was used to carry out the current GWAS analysis. A large GWAS published recently using European, African, and South Asian participants were used in performing the meta-analysis and replication analyses (N = 363,228 individuals) (10).…”

Section: Study Participantsmentioning

confidence: 99%

“…Despite the ample and prolonged sunshine in the Middle East regions, the highest prevalence of Vitamin D de ciency with major complications has been reported in these countries (22), with an incidence of up to 90% in Qatar (23), as in other Gulf states. Previous GWAS have focused primarily on identifying Vitamin D polymorphisms and evaluating the performance of aggregated models in the European population (8, [10][11][12]. No previous studies have been conducted on Middle Eastern individuals to date.…”

Section: Introductionmentioning

confidence: 99%

“…Compared with the European observations, we examined the frequency and effect size of high-impact alleles in genes linked to Vitamin D in the Qatari population. We combined the current GWAS results with a previous large GWAS data (10) consisting of 345,923 individuals in a meta-analysis. Based on this, we validated the replication of previously identi ed genetic determinants of 25(OH)D in the Middle Eastern population.…”

Section: Introductionmentioning

confidence: 99%

“…Based on this, we validated the replication of previously identi ed genetic determinants of 25(OH)D in the Middle Eastern population. Finally, we assessed the association between genetic markers related to Vitamin D and phenotype severity by using polygenic scores from the UK Biobank (10) and assessed their performance in the Qatari cohorts.…”

Section: Introductionmentioning

confidence: 99%

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Genetic Determinants of Vitamin D Deficiency in the Middle Eastern Qatari Population by a Genome-Wide Association Study

Nemer

Hindi

Al-Sarraj³

et al. 2023

Preprint

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Epidemiological studies have revealed that Middle Eastern countries have the highest incidence of Vitamin D deficiency with severe complications. However, the impact of Vitamin D polymorphisms and the performance of polygenic models have been studied primarily in European with little knowledge of the Middle Eastern. Here, we conducted the first genome-wide association study to identify genetic determinants of Vitamin D levels in Middle Eastern populations using a whole genome sequencing approach in 6,047 discovery subjects. We discovered a novel variant, rs2298850 (P-value = 1.71 × 10-08, effect size (Beta) = -0.1285), in a region of a known locus for the group-specific component gene (GC). We also confirmed the association of Vitamin D to several variants, including rs11723621 (P-value = 1.93 × 10-08, Beta = -0.12574) and rs4588 (P-value = 8.06 × 10-08, Beta = -0.1188) in the GC. A GWAS meta-analysis combining results from our Qatari cohort and previous European data identified novel variants in known loci, including rs67609747 and rs1945603 on chromosome 11. We found a moderately low heritability of Vitamin D (estimated at 18%) compared to Europeans. Finally, a low predictive performance of European ancestry-derived polygenic scores was observed when applied to the Qatari individuals. These results emphasize the diversity in the genetic architecture and its impact on preventive and precision medicine across different populations. Our findings offer novel perspectives on the physiological mechanisms and genetic factors contributing to the variation of Vitamin D levels in the Qatari population.

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Section: Meta-analysismentioning

confidence: 99%

Section: Study Participantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetic Determinants of Vitamin D Deficiency in the Middle Eastern Qatari Population by a Genome-Wide Association Study

Nemer

Hindi

Al-Sarraj³

et al. 2023

Preprint

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Associations between major psychiatric disorder polygenic risk scores and blood-based markers in UK biobank

Sewell

Jiménez-Sánchez

Shen

et al. 2021

Brain, Behavior, and Immunity

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Genome-wide Association Analysis of Schizophrenia and Vitamin D Levels Shows Shared Genetic Architecture and Identifies Novel Risk Loci

Jahołkowski

Hindley

Shadrin

et al. 2023

Schizophrenia Bulletin

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Low vitamin D (vitD) levels have been consistently reported in schizophrenia (SCZ) suggesting a role in the etiopathology. However, little is known about the role of underlying shared genetic mechanisms. We applied a conditional/conjunctional false discovery rate approach (FDR) on large, nonoverlapping genome-wide association studies for SCZ (N cases = 53 386, N controls = 77 258) and vitD serum concentration (N = 417 580) to evaluate shared common genetic variants. The identified genomic loci were characterized using functional analyses and biological repositories. We observed cross-trait SNP enrichment in SCZ conditioned on vitD and vice versa, demonstrating shared genetic architecture. Applying the conjunctional FDR approach, we identified 72 loci jointly associated with SCZ and vitD at conjunctional FDR < 0.05. Among the 72 shared loci, 40 loci have not previously been reported for vitD, and 9 were novel for SCZ. Further, 64% had discordant effects on SCZ-risk and vitD levels. A mixture of shared variants with concordant and discordant effects with a predominance of discordant effects was in line with weak negative genetic correlation (rg = −0.085). Our results displayed shared genetic architecture between SCZ and vitD with mixed effect directions, suggesting overlapping biological pathways. Shared genetic variants with complex overlapping mechanisms may contribute to the coexistence of SCZ and vitD deficiency and influence the clinical picture.

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Author Correction: Genetics of 35 blood and urine biomarkers in the UK Biobank

Cited by 11 publications

References 0 publications

Genetic Determinants of Vitamin D Deficiency in the Middle Eastern Qatari Population by a Genome-Wide Association Study

Genetic Determinants of Vitamin D Deficiency in the Middle Eastern Qatari Population by a Genome-Wide Association Study

Associations between major psychiatric disorder polygenic risk scores and blood-based markers in UK biobank

Genome-wide Association Analysis of Schizophrenia and Vitamin D Levels Shows Shared Genetic Architecture and Identifies Novel Risk Loci

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