Whole Genome Sequencing Identifies Four Novel Variants in the Epidermal Differentiation Complex That Increase Risk and Severity for Atopic Dermatitis

AbstractThe lack of Chinese population specific haplotype reference panel and whole genome sequencing resources has greatly hindered the genetics studies in the world’s largest population. Here we presented the NyuWa genome resource of 71.1M SNPs and 8.2M indels based on deep (26.2X) sequencing of 2,999 Chinese individuals, and constructed NyuWa reference panel of 5,804 haplotypes and 19.3M variants, which is the first publicly available Chinese population specific reference panel with thousands of samples. There were 25.0M novel variants in NyuWa genome resource, and 3.2M specific variants in NyuWa reference panel. Compared with other panels, NyuWa reference panel reduces the Han Chinese imputation error rate by the range of 30% to 51%. Population structure and imputation simulation tests supported the applicability of one integrated reference panel for both northern and southern Chinese. In addition, a total of 22,504 loss-of-function variants in coding and noncoding genes were identified, including 11,493 novel variants. These results highlight the value of NyuWa genome resource to facilitate genetics research in Chinese and Asian populations.

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269 Results from the largest whole-genome sequencing study of atopic dermatitis with extensive phenotyping

Journal of Investigative Dermatology ◽

10.1016/j.jid.2020.03.275 ◽

2020 ◽

Vol 140 (7) ◽

pp. S32

Author(s):

S. Smieszek

Keyword(s):

Atopic Dermatitis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome

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Whole genome sequencing data of multiple individuals of Pakistani descent

Scientific Data ◽

10.1038/s41597-020-00664-2 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Shahid Y. Khan ◽

Muhammad Ali ◽

Mei-Chong W. Lee ◽

Zhiwei Ma ◽

Pooja Biswas ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Sequence Data ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data ◽

Asian Populations ◽

Ethnic Populations ◽

Novel Variants ◽

Intergenic Regions

Abstract Here we report whole genome sequencing of four individuals (H3, H4, H5, and H6) from a family of Pakistani descent. Whole genome sequencing yielded 1084.92, 894.73, 1068.62, and 1005.77 million mapped reads corresponding to 162.73, 134.21, 160.29, and 150.86 Gb sequence data and 52.49x, 43.29x, 51.70x, and 48.66x average coverage for H3, H4, H5, and H6, respectively. We identified 3,529,659, 3,478,495, 3,407,895, and 3,426,862 variants in the genomes of H3, H4, H5, and H6, respectively, including 1,668,024 variants common in the four genomes. Further, we identified 42,422, 39,824, 28,599, and 35,206 novel variants in the genomes of H3, H4, H5, and H6, respectively. A major fraction of the variants identified in the four genomes reside within the intergenic regions of the genome. Single nucleotide polymorphism (SNP) genotype based comparative analysis with ethnic populations of 1000 Genomes database linked the ancestry of all four genomes with the South Asian populations, which was further supported by mitochondria based haplogroup analysis. In conclusion, we report whole genome sequencing of four individuals of Pakistani descent.

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Family-Based Whole Genome Sequencing Identified Novel Variants in ABCA5 Gene in a Patient with Idiopathic Ventricular Tachycardia

Pediatric Cardiology ◽

10.1007/s00246-020-02446-4 ◽

2020 ◽

Vol 41 (8) ◽

pp. 1783-1794

Author(s):

Zhanhui Du ◽

Shan Kuang ◽

Yong Li ◽

Peng Han ◽

Junnian Liu ◽

...

Keyword(s):

Ventricular Tachycardia ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Idiopathic Ventricular Tachycardia ◽

Novel Variants ◽

Family Based

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Large whole genome sequencing study identifies novel variants associated with intrinsic circadian period in humans

Sleep Medicine ◽

10.1016/j.sleep.2019.11.993 ◽

2019 ◽

Vol 64 ◽

pp. S356

Author(s):

S. Smieszek ◽

C. Polymeropoulos ◽

G. Birznieks ◽

M. Polymeropoulos

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Circadian Period ◽

Novel Variants

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Staphylococcus Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development

Science Translational Medicine ◽

10.1126/scitranslmed.aay4068 ◽

2020 ◽

Vol 12 (551) ◽

pp. eaay4068 ◽

Cited By ~ 3

Author(s):

Yuumi Nakamura ◽

Hiroki Takahashi ◽

Akiko Takaya ◽

Yuzaburo Inoue ◽

Yuki Katayama ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Atopic Dermatitis ◽

Quorum Sensing ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Skin Colonization ◽

Japanese Infants

Atopic dermatitis (AD) is commonly associated with colonization by Staphylococcus aureus in the affected skin. To understand the role of S. aureus in the development of AD, we performed whole-genome sequencing of S. aureus strains isolated from the cheek skin of 268 Japanese infants 1 and 6 months after birth. About 45% of infants were colonized with S. aureus at 1 month regardless of AD outcome. In contrast, skin colonization by S. aureus at 6 months of age increased the risk of developing AD. Acquisition of dysfunctional mutations in the S. aureus Agr quorum-sensing (QS) system was primarily observed in strains from 6-month-old infants who did not develop AD. Expression of a functional Agr system in S. aureus was required for epidermal colonization and the induction of AD-like inflammation in mice. Thus, retention of functional S. aureus agr virulence during infancy is associated with pathogen skin colonization and the development of AD.

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“Genomic and phenotypic characterization of Investigator Global Assessment (IGA) scale based endotypes in atopic dermatitis”

10.1101/2020.04.16.20058677 ◽

2020 ◽

Author(s):

Sandra P Smieszek ◽

Bartlomiej Przychodzen ◽

Sarah E Welsh ◽

Jennifer Brzezynski ◽

Alyssa Kaden ◽

...

Keyword(s):

Atopic Dermatitis ◽

Decision Tree ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Skin Disorder ◽

Global Assessment ◽

Phase Iii ◽

List Type ◽

Whole Genome ◽

Investigator Global Assessment

ABTRACTBackgroundAtopic dermatitis (AD) is a heritable and heterogeneous inflammatory chronic skin disorder. Utilizing decision tree/supervised learning of extensive clinical, molecular and genetic data, we aimed to define distinct AD endotypes.MethodsDeep phenotyping and whole-genome sequencing was performed on samples obtained from participants of EPIONE, a randomized-controlled phase III study in AD patients with severe pruritus comprising mild (23%), moderate (64%) and severe (13%) AD as determined by AD Investigator Global Assessment scale. Three categories of analysis were performed: clinical associations, lab value associations (EOS, IgE, cytokines) and genetic analysis of whole-genome sequencing dataResultsBased on a decision tree, we found that five clinical features from the SCORing Atopic Dermatitis (SCORAD) Index can accurately differentiate between IGA severities. We observe a significant difference between severity and eosinophil counts (p<0.001), IgE (p<0.001) and Filaggrin (FLG) LOF frequency (OR 2.3, CI 1.6-3.2, p<0.0001) as well as interleukin pathway genes, specifically IL5RA variants differentiating the groups.ConclusionOur results suggest significant differences between severity groups across a number of features appear to constitute distinct endotypes with likely distinct causative factors. Differing underlying pathophysiology’s indicate endotype knowledge is critical to help guide therapeutic approaches to AD.Capsule summaryAD is a heritable and heterogeneous skin disorder that makes the ‘one size fits all’ therapeutic approach suboptimal for patients with AD.We attempted to define AD endotypes based on clinical, molecular, and genetic characteristics. Clinical, CBC, and genetic associations all tend to suggest existence of separate endotypes.

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