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Table 1 Overview of the summary results statistics used in the Mendelian randomization analysis

From: Mendelian randomization analysis of factors related to ovulation and reproductive function and endometrial cancer risk

Phenotype

 

Data source

Study design

Population

Sample size

Phenotype definition

Inclusion/Exclusion criteria

Number of genetic variants

Genetic variant selection

Genetic Variants extracted

1. BMI

BMI [48, 49]

Exposure

UK Biobank and GIANT Consortium

Continous trait

European individuals

434,794

Phenotypes were rank inverse normalized transformed and residualized.

None stated

469

P < 10−8

Additional file 1: Table S1.

2. Ovulatory function

Years ovulating*

Exposure

Own GWAS in UKBB

Continous trait

European women

118,227

Years ovulating = years menstruating - years on pill - 0.75 * (live births + stillbirths)

Women with a history of hysterectomy before menopause (N = 12,539), who were not sure of their age at menopause due to their hysterectomy (N = 30,788), or early menopause (< 40 years; N = 3144) were excluded from the analysis.

11

p<5x10-8

Additional file 1: Table S2.

Age at Menarche [50, 51]

Exposure

ReproGen Consortium

Continous trait

European women

182,416

Self-reported age at menarche

Women who reported their age at menarche as <9 years or >17 years were excluded from the analysis.

110

p<5x10-8

Additional file 1: Table S3.

Age at Menopause [52, 53]

Exposure

ReproGen Consortium

Continous trait

European women

69,360

self-reported and defined as the age at last naturally occurring menstrual period followed by at least 12 consecutive months of amenorrhea.

Included women who were 40–60 years of age, excluding women with menopause induced by hysterectomy, bilateral ovariectomy, radiation or chemotherapy and those using hormone replacement therapy before menopause.

41

p<5x10-8

Additional file 1: Table S4.

3. Reproductive function

Number of live births* [54, 55]

Exposure

Own GWAS in UKBB

Continous trait

European women

237,768 women reporting how many children they mothered, 199,570 men reporting how many children they had fathered and 430,466 individuals reporting how many siblings they have.

Number of children mothered adjusted for paternal and child effect.

Participants reporting greater than 10 siblings (N = 1,720, 0.4%) or children (mothered N = 18, 0.007%; fathered N = 43, 0.02%) were recoded to have 10.

6

p<5x10-8

Additional file 1: Table S5.

Age at last live birth*

Exposure

Own GWAS in UKBB

Continous trait

European women

220,419

Age at last live birth was defined as the age of primiparous women at birth (for women who reported only one live birth) or the age at last live birth as reported by women who reported multiple live births.

Women with inconsistent reports of age at last live birth across the four data collection instances were excluded (n = 263).

19

p<5x10-8

Additional file 1: Table S6.

4. Oral contraceptive pill

We did not identify any genome-wide significant (p<5x10-8) SNPs associated with years taking the oral contraceptive pill, and this phenotype was therefore not taken forward in MR analyses.

Outcome

Endometrial Cancer [31]

Outcome

ECAC and E2C2 Consortium

Case/Control

European women

12,270 cases and 46,126 controlsa

Meta-analysis from cohorts using different case inclusion criteria

None stated

(10 as exposure in bidirectional MR)

 

Additional file 1: Table S7.

(Exposure in bidirectional MR)

  1. *Exposures considered primary exposures for the univariate Mendelian randomization analysis [31, 48,49,50,51,52,53,54,55]
  2. aExcluding UK Biobank. GWAS, genome-wide association study; BMI, body mass index; MR, Mendelian randomization; ECAC, Endometrial Cancer Association Consortium; E2C2, Epidemiology of Endometrial Cancer Consortium