Phenotyping | Tanigawa Lab

Hypometric genetics: Improved power in genetic discovery by incorporating quality control flags

Tue, 22 Oct 2024 00:00:00 +0000

We introduce “hypometric genetics,” an approach to investigate the genetic basis of binarized traits representing the presence of below-the-limit-of-quantification (BLQ) quality control indicators.

A cross-population atlas of genetic associations for 220 human phenotypes

Thu, 30 Sep 2021 00:00:00 +0000

Using a set of GWAS summary statistics of diseases characterized from both European (UK Biobank and FinnGen) and East Asian (Biobank Japan) populations, we dissected latent DeGAs components of multi-ethnic association summary statistics.

[Review in Japanese] 複数の表現型を用いた人類遺伝統計学の大規模情報解析 (Large-scale human genetic statistical inference with multiple phenotypes)

Fri, 23 Apr 2021 00:00:00 +0000

[invited review written in Japanese]. This is an invited review written in Japanese, published by the Japanese Society of Bioinformatics (JSBi).

日本語総説の執筆の機会をいただき、ゲノムワイド相関解析（GWAS）、ポリジェニック・リスク・スコア（polygenic risk score）、高次元データセットでの正則化つきの回帰モデル（penalized regression、Lasso 回帰など）に関する人類統計遺伝学の解析手法について執筆しました。

Genetics of 35 blood and urine biomarkers in the UK Biobank

Wed, 07 Apr 2021 00:00:00 +0000

Through UK Biobank-wide GWAS meta-analysis, we report > 10,000 GWAS associations (p < 5e-9) across 35 biomarkers and >5,700 loci. This includes > 450 large-effect (>0.1 s.d.) associations on protein-altering variants, which we highlight in a Fuji plot (gene symbols).

With FINEMAP, we identified >27,000 distinct signals in >5,000 regions across the 35 traits, of which >2,500 signals were fine-mapped to a single variant. We also trained sparse polygenic risk score (PRS) models with Lasso L1- penalized regression using the snpnet package.

To investigate the influence of the identified genetic basis on diseases, we performed single-variant PheWAS, PRS-PheWAS, and causal inference. Motivated by those results, we developed multi-PRS by combining a single-trait PRS model of disease with that of 35 biomarkers.

When we compare the predictive performance, multi-PRS showed improvements over single-trait snpnet PRS across many diseases, which we also replicated in FinnGen, suggesting both large case numbers and multi-trait modeling might complementarily contribute to improving the power.

This work was led by Nasa Sinnott-Armstrong, myself, and Dr. Manuel A. Rivas, with many contributions from colleagues. We thank UK Biobank, FinnGen, their participants, amazing collaborators, and colleagues, as well as funding.

Cardiac Imaging of Aortic Valve Area From 34287 UK Biobank Participants Reveals Novel Genetic Associations and Shared Genetic Comorbidity With Multiple Disease Phenotypes

Fri, 30 Oct 2020 00:00:00 +0000

Assessing Digital Phenotyping to Enhance Genetic Studies of Human Diseases

Thu, 07 May 2020 00:00:00 +0000

Large-scale population-based genotyped biobanks with dense phenotypic information provide opportunities for genetic analysis at scale.

Significant shared heritability underlies suicide attempt and clinically predicted probability of attempting suicide

Fri, 04 Jan 2019 00:00:00 +0000

Using two independent datasets from genotyped cohorts (UK Biobank and electronic medical record (EMR) in Vanderbilt University Medical Center), we quantified the heritability estimates of suicide attempts.