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- Jia, X. M., et al.
(författare)
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Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26:9
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 x 10(-4)), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.
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| 2. |
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| 3. |
- Goes, Fernando S, et al.
(författare)
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Exome Sequencing of Familial Bipolar Disorder.
- 2016
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 73:6, s. 590-7
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Tidskriftsartikel (refereegranskat)abstract
- Complex disorders, such as bipolar disorder (BD), likely result from the influence of both common and rare susceptibility alleles. While common variation has been widely studied, rare variant discovery has only recently become feasible with next-generation sequencing.
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| 4. |
- Xiao, Wenming, et al.
(författare)
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Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1141-1150
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Tidskriftsartikel (refereegranskat)abstract
- Recommendations are given on optimal read coverage and selection of calling algorithm to maximize the reproducibility of cancer mutation detection in whole-genome or whole-exome sequencing. Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.
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| 5. |
- Behnamian, Sara, et al.
(författare)
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Temporal population structure, a genetic dating method for ancient Eurasian genomes from the past 10,000 years
- 2022
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Ingår i: Cell reports methods. - : Elsevier BV. - 2667-2375. ; 2:8
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Tidskriftsartikel (refereegranskat)abstract
- Radiocarbon dating is the gold standard in archeology to estimate the age of skeletons, a key to studying their origins. Many published ancient genomes lack reliable and direct dates, which results in obscure and contradictory reports. We developed the temporal population structure (TPS), a DNA-based dating method for genomes ranging from the Late Mesolithic to today, and applied it to 3,591 ancient and 1,307 modern Eurasians. TPS predictions aligned with the known dates and correctly accounted for kin relationships. TPS dating of poorly dated Eurasian samples resolved conflicting reports in the literature, as illustrated by one test case. We also demonstrated how TPS improved the ability to study phenotypic traits over time. TPS can be used when radiocarbon dating is unfeasible or uncertain or to develop alternative hypotheses for samples younger than 10,000 years ago, a limitation that may be resolved over time as ancient data accumulate.
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