Table 1 Candidate traits associated with both exposure and outcome.

From: Exploiting horizontal pleiotropy to search for causal pathways within a Mendelian randomization framework

Outlier SNPs

Nearest gene

Category

Phenotypesa

N SNPsb

Beta (95% CI)c

Empirical analysis 1: systolic blood pressure (mmHg) on coronary heart disease (Odds ratio)

rs3184504

SH2B3

Early development

Birth weight of first child

40

−0.312 (−0.498, −0.126)

Anthropometric measures

Standing height

577

−0.208 (−0.264, −0.152)

Lipid

LDL cholesterol

78

0.393 (0.290, 0.497)

HDL cholesterol

86

−0.172 (−0.288, −0.055)

Total cholesterol

86

0.378 (0.271, 0.484)

rs9349379

PHACTR

Medications

Self-reported status of ibuprofen intake

2

−16.726 (−37.262, −3.811)

Empirical analysis 2: urate (mg/dl) and coronary heart disease (Odds ratio)

rs653178

ATXN2

Early development

Birth weight of first child

31

0.347 (0.065, 0.628)

Birth weight

40

−0.312 (−0.498, −0.126)

Anthropometric measures

Comparative height size at age 10

357

−0.248 (−0.342, −0.154)

Hip circumference

275

0.131 (0.030, 0.231)

Impedance of arm (left)

305

−0.263 (−0.380, −0.145)

Standing height

577

−0.208 (−0.264, −0.152)

Lipid

HDL cholesterol

78

0.393 (0.290, 0.497)

LDL cholesterol

86

−0.172 (−0.288, −0.055)

Total cholesterol

86

0.378 (0.271, 0.484)

Disease

hypothyroidism/myxoedema (Self-reported)

77

0.847 (0.211, 1.483)

Smoking

Past tobacco smoking

41

−0.265 (−0.500, −0.029)

Medications

Treatment/medication: levothyroxine sodium

51

1.231 (0.270, 2.191)

rs642803

OVOL1

Anthropometric measures

Waist circumference

218

0.458 (0.352, 0.563)

Empirical analysis 3: sleep duration (hour/night) and schizophrenia (Odds ratio)

rs7764984

HIST1H2BJ

Disease

Malabsorption/coeliac disease (self-reported)

11

−8.401 (−12.842, −3.961)

rs13107325

SLC39A8

Anthropometric measures

Impedance of leg (left)

282

0.179 (0.047, 0.311)

Memory

Prospective memory result

2

4.493 (1.851, 7.135)

Empirical analysis 4: years of schooling (years) and body mass index (kg/m2)

rs6882046

LINC00461

Drinking

Alcohol intake frequency

31

0.347 (0.065, 0.628)

rs4800490

NPC1

Drinking

Alcohol intake frequency

31

0.347 (0.065, 0.628)

Exercise

Usual walking pace

22

−1.595 (−2.364, −0.825)

rs8049439

ATXN2L

Drinking

Alcohol intake frequency

31

0.347 (0.065, 0.628)

  1. SNP single-nucleotide polymorphism, VLDL very low-density lipoprotein, HDLC high-density lipoprotein cholesterol, LDLC low-density lipoprotein cholesterol, N SNPs number of SNPs, CI confidence interval.
  2. aCandidate traits that are associated with outliers (p < 5 × 10−8) and both exposure and outcome are listed. The listed traits were used in the adjusted model to investigate whether they are associated with the hypothesised outcome.
  3. bThe number of SNPs used for two-sample MR analysis of candidate traits on the outcome.
  4. cThe results were presented as IVW beta coefficient (95% CI), derived from two-sample MR analyses. Empirical analysis 1: systolic blood pressure (mmHg) and coronary heart disease (log odds); Empirical analysis 2: urate (mg/dl) and coronary heart disease (log odds); Empirical analysis 3: sleep duration (hour/night) and schizophrenia (log odds); Empirical analysis 4: years of schooling (years) and body mass index (kg/m2).
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