Unravelling the genetic architecture of human complex traits through whole genome sequencing

Bocher, Ozvan; Willer, Cristen J.; Zeggini, Eleftheria

doi:10.1038/s41467-023-39259-x

Cited by 9 publications

(3 citation statements)

References 36 publications

(44 reference statements)

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“…Second, the gold standard genetic test for this purpose is whole genomic sequencing with high cover and depth. Facing the size of our cohort and limited financial support, we decided to combine the whole exome sequencing with low-pass whole genome sequencing to allow for PRS calculation, a successful strategy used by previous studies and supported by guidelines [ 26 , 27 , 63 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil

Alves de Oliveira,

de Menezes Neves,

de Figueiredo Oliveira

et al. 2024

PLoS ONE

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Atherosclerotic Cardiovascular Disease (ASCVD) represents the leading cause of death worldwide, and individual screening should be based on behavioral, metabolic, and genetic profile derived from data collected in large population-based studies. Due to the polygenic nature of ASCVD, we aimed to assess the association of genomics with ASCVD risk and its impact on the occurrence of acute myocardial infarction, stroke, or peripheral artery thrombotic-ischemic events at population level. CardioVascular Genes (CV-GENES) is a nationwide, multicenter, 1:1 case-control study of 3,734 patients in Brazil. Inclusion criterion for cases is the first occurrence of one of the ASCVD events. Individuals without known ASCVD will be eligible as controls. A core lab will perform the genetic analyses through low-pass whole genome sequencing and whole exome sequencing. In order to estimate the independent association between genetic polymorphisms and ASCVD, a polygenic risk score (PRS) will be built through a hybrid approach including effect size of each Single Nucleotide Polymorphism (SNP), number of effect alleles observed, sample ploidy, total number of SNPs included in the PRS, and number of non-missing SNPs in the sample. In addition, the presence of pathogenic or likely pathogenic variants will be screened in 8 genes (ABCG5, ABCG8, APOB, APOE, LDLR, LDLRAP1, LIPA, PCSK9) associated with atherosclerosis. Multiple logistic regression will be applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI), and population attributable risks will be calculated. Clinical trial registration: This study is registered in clinicaltrials.gov (NCT05515653).

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Section: Discussionmentioning

confidence: 99%

Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil

Alves de Oliveira,

de Menezes Neves,

de Figueiredo Oliveira

et al. 2024

PLoS ONE

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“…With the advancement of bioinformatic tools and sequencing technologies, whole-genome analysis has allowed researchers to comprehensively explore genetic variation, genomic architecture, and their associated pathways underlying a complex trait ( Almasy 2012 ; Bocher et al . 2023 ).…”

Section: Discussionmentioning

confidence: 99%

A chromosome-level genome assembly of the Asian house martin implies potential genes associated with the feathered-foot trait

Chan,

Lu,

Kuo

et al. 2024

G3: Genes, Genomes, Genetics

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The presence of feathers is a vital characteristic among birds, yet most modern birds had no feather on their feet. The discoveries of feathers on the hind limbs of basal birds and dinosaurs have sparked an interest in the evolutionary origin and genetic mechanism of feathered feet. However, the majority of studies investigating the genes associated with this trait focused on domestic populations. Understanding the genetic mechanism underpinned feathered-foot development in wild birds is still in its infancy. Here, we assembled a chromosome-level genome of the Asian house martin (Delichon dasypus) using the long-read HiFi sequencing approach to initiate the search for genes associated with its feathered feet. We employed the whole genome alignment of D. dasypus with other swallow species to identify high-SNP regions and chromosomal inversions in the D. dasypus genome. After filtering out variations unrelated to D. dasypus evolution, we found six genes related to feather development near the high-SNP regions. We also detected three feather development genes in chromosomal inversions between the Asian house martin and the barn swallow genomes. We discussed their association with the WNT, BMP and FGF pathways and their potential roles in feathered-foot development. Future studies are encouraged to utilize the D. dasypus genome to explore the evolutionary process of the feathered-foot trait in avian species. This endeavor will shed light on the evolutionary path of feathers in birds.

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“…Whole-genome sequencing (WGS) datasets are invaluable resources for human genetic and biomedical research ( 1 ). Through comprehensive profiling of genetic variants, WGS data have enabled various in-depth analyses.…”

Section: Introductionmentioning

confidence: 99%

Decoding triancestral origins, archaic introgression, and natural selection in the Japanese population by whole-genome sequencing

Liu,

Koyama,

Tomizuka

et al. 2024

Sci. Adv.

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We generated Japanese Encyclopedia of Whole-Genome/Exome Sequencing Library (JEWEL), a high-depth whole-genome sequencing dataset comprising 3256 individuals from across Japan. Analysis of JEWEL revealed genetic characteristics of the Japanese population that were not discernible using microarray data. First, rare variant–based analysis revealed an unprecedented fine-scale genetic structure. Together with population genetics analysis, the present-day Japanese can be decomposed into three ancestral components. Second, we identified unreported loss-of-function (LoF) variants and observed that for specific genes, LoF variants appeared to be restricted to a more limited set of transcripts than would be expected by chance, with PTPRD as a notable example. Third, we identified 44 archaic segments linked to complex traits, including a Denisovan-derived segment at NKX6-1 associated with type 2 diabetes. Most of these segments are specific to East Asians. Fourth, we identified candidate genetic loci under recent natural selection. Overall, our work provided insights into genetic characteristics of the Japanese population.

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Unravelling the genetic architecture of human complex traits through whole genome sequencing

Cited by 9 publications

References 36 publications

Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil

Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil

A chromosome-level genome assembly of the Asian house martin implies potential genes associated with the feathered-foot trait

Decoding triancestral origins, archaic introgression, and natural selection in the Japanese population by whole-genome sequencing

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