The importance of distinguishing between the odds ratio and the incidence rate ratio in GWAS

BMC Medical Genetics
Berit Lindum WaltoftAsger Hobolth

Abstract

In recent years, genome wide association studies have identified many genetic variants that are consistently associated with common complex diseases, but the amount of heritability explained by these risk alleles is still low. Part of the missing heritability may be due to genetic heterogeneity and small sample sizes, but non-optimal study designs in many genome wide association studies may also have contributed to the failure of identifying gene variants causing a predisposition to disease. The normally used odds ratio from a classical case-control study measures the association between genotype and being diseased. In comparison, under incidence density sampling, the incidence rate ratio measures the association between genotype and becoming diseased. We estimate the differences between the odds ratio and the incidence rate ratio under the presence of events precluding the disease of interest. Such events may arise due to pleiotropy and are known as competing events. In addition, we investigate how these differences impact the association test. We simulate life spans of individuals whose gene variants are subject to competing events. To estimate the association between genotype and disease, we applied classical case-control st...Continue Reading

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Citations

Jan 31, 2019·JAMA Psychiatry·Katherine L MuslinerUNKNOWN Bipolar Disorder Working Group of the Psychiatric Genomics Consortium
Feb 26, 2020·Briefings in Bioinformatics·Daniel Toro-DomínguezPedro Carmona-Sáez
Feb 21, 2021·Seminars in Thoracic and Cardiovascular Surgery·Yujiro YokoyamaToshiki Kuno

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