# Multiple phenotype association tests based on sliced inverse regression

**Authors:** Wenyuan Sun, Kyongson Jon, Wensheng Zhu

PMC · DOI: 10.1186/s12859-024-05731-8 · BMC Bioinformatics · 2024-04-04

## TL;DR

This paper introduces a new statistical method for analyzing multiple traits and genetic variants, which is more efficient and accurate than existing approaches.

## Contribution

A novel sliced inverse regression-based association test is proposed for joint analysis of multiple phenotypes and genetic variants.

## Key findings

- The proposed SIR-based method outperforms existing methods in both low- and high-dimensional settings.
- The method achieves higher efficiency and maintains correct type I error rates in genetic association studies.

## Abstract

Joint analysis of multiple phenotypes in studies of biological systems such as Genome-Wide Association Studies is critical to revealing the functional interactions between various traits and genetic variants, but growth of data in dimensionality has become a very challenging problem in the widespread use of joint analysis. To handle the excessiveness of variables, we consider the sliced inverse regression (SIR) method. Specifically, we propose a novel SIR-based association test that is robust and powerful in testing the association between multiple predictors and multiple outcomes.

We conduct simulation studies in both low- and high-dimensional settings with various numbers of Single-Nucleotide Polymorphisms and consider the correlation structure of traits. Simulation results show that the proposed method outperforms the existing methods. We also successfully apply our method to the genetic association study of ADNI dataset. Both the simulation studies and real data analysis show that the SIR-based association test is valid and achieves a higher efficiency compared with its competitors.

Several scenarios with low- and high-dimensional responses and genotypes are considered in this paper. Our SIR-based method controls the estimated type I error at the pre-specified level \documentclass[12pt]{minimal}
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## Full-text entities

- **Genes:** TG (thyroglobulin) [NCBI Gene 7038] {aka AITD3, TGN}, PCSK5 (proprotein convertase subtilisin/kexin type 5) [NCBI Gene 5125] {aka PC5, PC6, PC6A, SPC6}, APOC1 (apolipoprotein C1) [NCBI Gene 341] {aka APOC1B, Apo-CI, ApoC-I, apo-CIB, apoC-IB}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, TOMM40 (translocase of outer mitochondrial membrane 40) [NCBI Gene 10452] {aka C19orf1, D19S1177E, PER-EC1, PEREC1, TOM40}
- **Diseases:** hypothyroidism (MESH:D007037), MCI (MESH:D060825), AD (MESH:D000544), amyloid (MESH:C000718787), amyloid deposition (MESH:D058225), autoimmune disorders (MESH:D001327), cognitive impairment (MESH:D003072), dementia (MESH:D003704), cerebral (MESH:D002547)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs394819, rs8106922, rs769449, rs1081101, rs10524523, rs445925, rs405509, rs1160985

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10996256/full.md

## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC10996256/full.md

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Source: https://tomesphere.com/paper/PMC10996256