Ordinal GWAS analysis of the frailty phenotype identified a novel locus at 12q22 that underscores the role of the neurological and immune systems.

Sayem Borhan, Le Minh An Nguyen, Marie Pigeyre, Guillaume Pare, Jonathan Adachi, Alexandra Papaioannou, Lauren E Griffith, Lehana Thabane, Parminder Raina

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Article in npj aging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

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5 · Who and what money

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9 authors.

Sayem BorhanDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada. borhana@mcmaster.ca.

Le Minh An NguyenDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.

Marie PigeyreDepartment of Medicine, McMaster University, Hamilton, ON, Canada.

Guillaume PareDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.

Jonathan AdachiDepartment of Medicine, McMaster University, Hamilton, ON, Canada.

Alexandra PapaioannouDepartment of Medicine, McMaster University, Hamilton, ON, Canada.

Lauren E GriffithDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.

Lehana ThabaneDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.

Parminder RainaDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Frailty is a complex trait that significantly increases the risk for negative health consequences, including hospitalization and disability. However, the evidence regarding the genetic basis of frailty phenotype (FP) is very limited. We conducted a genome-wide association study (GWAS) on FP using the data from the Canadian Longitudinal Study on Aging (CLSA). We classified the participants as non-frail, pre-frail, and frail, and performed a GWAS utilizing the ordinal logistic regression adjusted for sex, number of chronic conditions, and 10 principal components. Several post-GWAS analyses, including cis-eQTL analyses, were conducted to investigate the potential functional significance. In total, 23,105 participants and more than 8 million imputed SNPs were included in the analysis. The average age was 63 years, and 50.35% of the participants were female. Most participants were non-frail (11,297; 48.89%) or pre-frail (10,261; 44.41%), whereas only 1547 (6.70%) were frail. One novel genomic variant (rs147311617) at the 12p22 locus was found significant at the level of genome-wide significance (p = 4.98×10

Identifiers

PMID42020437

DOI10.1038/s41514-026-00363-z

PMCPMC13103308

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