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Table 1 Baseline characteristics of the study participants

Number

J-MICC (all)

Men

Women

14,073

6,329

7,744

Women (%)

55.0

Age (years)

54.8±9.4

55.4±9.3

54.3±9.4

<0.001

Confections intake (KJ/day)

198±142

179±162

243±177

<0.001

Total energy intake (KJ/day)

7,135±1,490

7,974±1,514

6,431±1,074

<0.001

Protein intake (% energy)

12.7±2.0

11.8±1.8

13.3±1.9

<0.001

Fat intake (% energy)

23.8± 6.4

20.5±5.4

26.6±5.9

<0.001

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Carbohydrate intake (% energy)

55.8±6.2

56.8±6.7

54.9±5.6

<0.001

Alcohol intake (g/day)

9.4±16.3

17.3±20.2

2.9±7.6

<0.001

BMI (kg/m2)

23.1± 3.3

23.8±3.2

22.5±3.4

<0.001

Values are shown as the mean ± SD, or as percentages. P values are by Student’s t-tests.

BMI=Body Mass Index, J-MICC= the Japan Multi-Institutional Collaborative Cohort study

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Table 2 SNPs with the 10 lowest P-values that were associated with confections intake in discovery samples (J-MICC study, N=14,073), adjusted for age,

sex, PCA.

SNP

Chr

Position

Gene

EA

NEA

EAFR

BETA

SE

rs11066001

12

112119171

BRAP

0.2652

1.6672

0.1471

1.20E-29

rs11066015

12

112168009

ACAD10

0.2559

1.7044

0.1477

1.13E-30

rs4646776

12

112230019

ALDH2

0.256

1.6999

0.1476

1.43E-30

rs671

12

112241766

ALDH2

0.2563

1.7045

0.1474

8.62E-31

0.2604

1.6924

0.1492

1.09E-29

ADAM1A/

rs78069066

12

112337924

MAPKAPK5/

TMEM116

rs11066132

12

112468206

NAA25

0.2526

1.7512

0.1531

3.63E-30

rs116873087

12

112511913

NAA25

0.2562

1.7193

0.1524

2.12E-29

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rs12231737

12

112574616

TRAFD1

0.2619

1.6963

0.1509

3.46E-29

rs144504271

12

112627350

HECTD4

0.2581

1.6797

0.1503

6.86E-29

rs2074356

12

112645401

HECTD4

0.2325

1.6933

0.1524

1.43E-28

Genome-wide analyses among the 8,504,983 variants adjusted for age, sex, total energy intake, and PCA 1-3, identified 418 SNPs on chromosome 12 that were

associated with confections intake with genome-wide significance (P<5×10-8).

SNP=single nucleotide polymorphism, Chr=chromosome; Chromosomal position (GRCh37/hg19), EA=effect allele, NEA=non-effect allele, EA FR=effect

allele frequency; Beta=effect size; SE=standard error of effect size, J-MICC= the Japan Multi-Institutional Collaborative Cohort study,

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Table 3 Replication analysis using the J-MICC samples for SNPs that were associated with confections intake in previous studies

Gene

TAS1R2

TAS1R3

GNAT3

SNP

Chr:Posotion

EA

NEA

EAFR

BETA

SE

rs12033832

1:19166294

0.473

0.330

0.130

0.011

rs3935570

1:19167371

0.066

-0.042

0.261

0.871

rs35874116

1:19181393

0.113

-0.102

0.203

0.616

rs121377303

NA

rs75346183

4:162614852

0.208

0.211

0.160

0.187

rs97017963

NA

rs307355

1:1265154

0.806

-0.117

0.161

0.467

rs35744813

1:1265460

0.805

-0.120

0.161

0.457

rs7792845

7:80151369

0.785

0.228

0.163

0.163

rs940541

7:80150594

0.828

0.076

0.170

0.653

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rs1107660

7:80150131

0.821

0.061

0.167

0.713

rs1107657

7:80150018

0.821

0.061

0.167

0.713

rs1524600

7:80138303

0.114

0.006

0.202

0.975

rs6467217

7:80138178

0.114

0.006

0.201

0.976

rs6970109

7:80138074

0.114

0.006

0.201

0.976

rs6975345

7:80123999

0.111

-0.047

0.203

0.817

rs10242727

7:80119730

0.111

-0.042

0.204

0.837

rs6467192

7:80107798

0.111

-0.037

0.204

0.856

rs6961082

7:80100969

0.099

-0.001

0.214

0.995

GLUT2

rs5400

3:170732300

0.020

-0.712

0.455

0.118

FGF21

rs838133

19:49259529

0.973

-0.138

0.676

0.839

rs11642841

16:53845487

0.098

-0.016

0.217

0.940

FTO

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We carried out a replication study on the 20 identified loci (including sweet taste receptor gene family) associated with sweets intake.

SNP=single nucleotide polymorphism, Chr=chromosome, Position=chromosomal position (GRCh37/hg19), EA=effect allele, NEA=non-effect allele,

EAF=effect allele frequency, Beta=effect size, SE=standard error of effect size

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Figure legends

Figure 1.

A quantile-quantile plot (black) of genome-wide association tests. The x-axis indicates the expected

-log10 P-values under the null hypothesis. The y-axis shows the observed-log10P-values calculated by a

linear regression model using PLINK [23]. The

line represents y=x, which corresponds to the null hypothesis. The gray shaded area shows the 95%

confidence interval of the null hypothesis. The inflation factor (λ) is the median of the observed test

statistics divided by the median of the expected test statistics. An R package for creating the Q-Q plot,

GWAS Tools, was used [32].

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Figure 2.

Genome-wide association signals. The x-axis represents chromosomal positions and the y-axis

represents -log10P-values calculated by a linear model association analysis. The software, qqman, was

used [33].

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Figure 3.

A quantile-quantile plot (black) of genome-wide association tests. The x-axis indicates the expected

-log10 P-values under the null hypothesis. The y-axis shows the observed-log10P-values calculated by a

linear regression model using PLINK [23]. The line represents y=x, which corresponds to the null

hypothesis. The gray shaded area shows the 95% confidence interval of the null hypothesis. The

inflation factor (λ) is the median of the observed test statistics divided by the median of the expected test

statistics. An R package for creating the Q-Q plot, GWAS Tools, was used [32].

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Accepted manuscript

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