Evidence map›Paper›PMID 35421149›Full record

ArticlePloS one2022

Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults.

A C Pronk, L J Seppala, K Trajanoska, N Stringa, B van de Loo, L C P G M de Groot, N M van Schoor, F Koskeridis, G Markozannes, E Ntzani and 4 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.4field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Genetic determinants of antidepressant and antipsychotic drug response.European archives of psychiatry and clinical neuroscience · 2025
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 3 countries.

A C PronkDepartment of Internal Medicine, Section of Geriatric Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0001-5154-2369
L J SeppalaDepartment of Internal Medicine, Section of Geriatric Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
K TrajanoskaDepartment of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
N StringaDepartment of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
B van de LooDepartment of Internal Medicine, Section of Geriatric Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
L C P G M de GrootDepartment of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands.
N M van SchoorDepartment of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
F KoskeridisDepartment of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.ORCID 0000-0002-1253-7556
G MarkozannesDepartment of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.ORCID 0000-0001-8481-579X
E NtzaniDepartment of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
A G UitterlindenDepartment of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
F RivadeneiraDepartment of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
B H StrickerDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
N van der VeldeDepartment of Internal Medicine, Section of Geriatric Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Amsterdam University Medical Centers · NLErasmus MC · NLUniversity of Ioannina · GRWageningen University & Research · NL

Funding

British Heart FoundationDepartment of HealthHSRD VA CDA 10-014Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Wellcome Trust
6 · The paper itself

Abstract

backgroundAntidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users.

methodsThe association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated.

resultsIn antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26-0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17-3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07-2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05-3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01-1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92-1.00).

conclusionThis is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention.

Indexed as

Antidepressive AgentsGenome-Wide Association StudyAgedGenotypeHumansMiddle AgedPolymorphism, GeneticPolymorphism, Single NucleotideProspective StudiesAntidepressive Agents

Identifiers

PMID35421149
PMCPMC9009709
OpenAlexW4224018024

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