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Test-statistic inflation in methylome-wide association studies.

ABSTRACT: Recent years have seen a surge of methylome-wide association studies (MWAS). We observed that many of these studies suffer from test statistic inflation that is most likely caused by commonly used quality control (QC) pipelines not going far enough to remove technical artefacts. To support this claim, we reanalysed GEO datasets with an improved QC pipeline that reduced test-statistic inflation parameter lambda from the original mean/median of 20.16/15.17 to 3.07/1.14. Furthermore, the mean/median number of methylome-wide significant findings was reduced by 65,688/57,805 loci after more thorough QC. To avoid such false positives we argue for more extensive QC and that reporting the test-statistic inflation parameter lambda become standard for all MWAS allowing readers to better assess the risk of false discoveries.

SUBMITTER: Guintivano J

PROVIDER: S-EPMC7595582 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Test-statistic inflation in methylome-wide association studies.

Guintivano Jerry J Shabalin Andrey A AA Chan Robin F RF Rubinow David R DR Sullivan Patrick F PF Meltzer-Brody Samantha S Aberg Karolina A KA van den Oord Edwin J C G EJCG

Epigenetics 20200519 11

Recent years have seen a surge of methylome-wide association studies (MWAS). We observed that many of these studies suffer from test statistic inflation that is most likely caused by commonly used quality control (QC) pipelines not going far enough to remove technical artefacts. To support this claim, we reanalysed GEO datasets with an improved QC pipeline that reduced test-statistic inflation parameter lambda from the original mean/median of 20.16/15.17 to 3.07/1.14. Furthermore, the mean/media ...[more]

PMID: 32425094

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