Skip to main content

Table 1 Characteristics of the current Mendelian randomization studies conducted for modifiable environmental exposures and RA

From: Modifiable environmental exposure and risk of rheumatoid arthritis—current evidence from genetic studies

Author

Year

Exposure

Outcome

Results

Trait

Genetic data

Ancestry

#IV

Trait

Genetic data

Ancestry

Bae and Lee

2018

Vitamin D

Summary statistics from two vitamin D GWAS. One consisted of 3538 individuals with replication in an additional 2151 individuals. The other consisted of 4501 persons from five cohorts.

Asian Indian + European

3

RA onset

Meta-GWAS of 5539 autoantibody-positive RA and 20,169 controls with replication in an independent set of 6768 RA and 8806 controls

European

No significant associations

Viatte et al.

2014

Vitamin D

SNPs in four vitamin D metabolism genes (GC, DHCR7/NADSYN1, CYP2R1 and CYP24A1) associated at genome-wide significance with circulating vitamin D levels.

European

20

RA radiological outcome

1433 patients with 2164 X-rays from the Norfolk Arthritis Register (NOAR) and in 443 RA patients with 2924 X-rays from the Early Rheumatoid Arthritis Study (ERAS)

European

No significant associations

Yarwood et al.

2013

Vitamin D

SNPs in three vitamin D metabolism genes (GC, DHCR7/NADSYN1, and CYP2R1) associated at genome-wide significance with circulating vitamin D levels.

European

6

RA treatment response

1396 RA patients from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS)

European

No significant associations

Bae and Lee

2018

Body mass index

Meta-GWAS for BMI in 322,154 individuals from the GIANT consortium.

European

68

RA onset

UK Biobank GWAS of 337,159 individuals (7480 RA cases and 329,679 controls)

European

Both IVW and median based methods showed evidence to support a causal association between BMI and RA

Qian et al.

2020

Smoking

The IV and the genetic association estimates for smoking initiation and lifetime smoking were obtained from a GWAS metaanalysis including 1,232,091 individuals and a GWAS of 462,690 individuals.

European

367, 124

RA onset

GWAS including 14,361 RA cases and 43,923 controls

European

Genetic predisposition to smoking initiation and lifetime smoking significantly increased RA risk

Bae and Lee

2019

Alcohol consumption

GWAS for alcohol intake frequency (increase) from 336,965 individuals included in the UK Biobank.

European

24

RA onset

Meta-GWAS of 5539 autoantibody-positive RA and 20,169 controls with replication in an independent set of 6768 RA and 8806 controls

European

No significant associations

Bae and Lee

2018

Coffee consumption

Summary data of meta-GWAS on coffee intake from 8 Caucasian cohorts (n = 18,176) and meta-GWAS of predominately regular-type coffee consumption (cups per day) among coffee consumers (n = 91,462).

European

4

RA onset

Meta-GWAS of 5539 autoantibody-positive RA and 20,169 controls with replication in an independent set of 6768 RA and 8806 controls

European

Genetic predisposition to coffee consumption significantly increased RA risk

Yuan et al.

2020

Iron

A large GWAS of 48,972 individuals, four measures, serum iron, serum transferrin saturation, ferritin, and transferrin.

European

5, 5, 6, 8

RA onset

Large-scale meta-analysis of over 20 GWASs including 14,361 RA cases and 43,923 controls

European

Consistent across four iron biomarkers, genetically high iron status was inversely associated with RA

Cheng et al.

2019

Mineral nutrients

Ca-related genetic variation was derived from 17 population-based GWAS (n = 39,400). The genetic variation of Mg is the result of a GWAS (n = 15,366) from the CHARGE Alliance. The Fe-related genetic variation was the GWAS result in 8 populations (n = 48,972). The genetic variation with Cu and Zn concentrations in erythrocytes were derived from the Queensland Institute of Medicine’s twins and their families (n = 2603).

Mixed population

8, 5, 14, 2, 3

RA onset

Meta-GWAS for 10 million RA-related SNPs were evaluated in a total of > 100,000 subjects of European and Asian ancestry (29,880 RA casesand 73,758 controls)

Asian and European

No consistent significant results between mineral nutrients and RA

Zhao et al.

2018

PUFA

Strong, independent genetic predictors of linoleic acid using the three most significant uncorrelated SNPs and seven uncorrelated SNPs in genes (FADS1, FADS2, and NTAN1) relevant to PUFA metabolism from a GWAS in 8631 adults.

European

10

RA onset

GWAS including 14,361 RA cases and 43,923 controls

European

Genetically instrumented LA was inversely associated with RA

Inamo

2019

Gut microbiome

GWASs for gut microbiome (totally 3326 individuals)

European

26

RA onset

GWAS including 14,361 RA cases and 43,923 controls

European

No significant associations

Bae and Lee

2018

Education

A UK Biobank GWAS (n = 293,723) on years of education

European

49

RA onset

Meta-GWAS of 5539 autoantibody-positive RA and 20,169 controls with replication in an independent set of 6768 RA and 8806 controls

European

The IVW method instructed an inverse causative relationship between years of education and RA