Dataset of allele and genotype frequencies of five polymorphisms candidate genes analyzed for association with body mass index in Russian women.

The dataset represents the raw data (supplementary Table), frequencies of alleles and genotypes for five single nucleotide polymorphisms (SNPs) of 5 genes, rs1514175 TNNI3K , rs713586 RBJ, rs887912 FANCL , rs2241423 MAP2K5 , and rs12444979 GPRC5B in Russian women ( Table 1 ). These SNPs were associated with body mass index (BMI) in previously published genome-wide and candidate gene association studies [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] ]. The dataset frequencies of the SNP alleles and genotypes were divided into five groups according to the BMI of the participants: all samples, underweight (BMI30.00). No significant differences in the allele and genotype frequencies between the groups with underweight (BMI30.00) (p > 0.05) were determined. Table 1 The frequencies of alleles and genotypes for single nucleotide polymorphisms (SNPs) rs1514175 TNNI3K , rs713586 RBJ, rs887912 FANCL , rs2241423 MAP2K5 , rs12444979 GPRC5B in the sample of Russian women. Table 1 SNP genotype or allele All (n = 716) Body mass index n frequency Mean, kg/m 2 underweight (BMI30.00) (n = 72) n frequency n frequency n frequency n frequency rs1514175 TNNI3K CC 275 0.3841 23.84 ± 4.46 21 0.5250 173 0.3888 59 0.3710 22 0.3056 CT 331 0.4623 24.16 ± 4.37 11 0.2750 206 0.4629 70 0.4403 44 0.6111 TT 110 0.1536 23.13 ± 3.70 8 0.2000 66 0.1483 30 0.1887 6 0.0833 C 881 0.6152 – 53 0.6625 552 0.6202 188 0.5912 88 0.6111 T 551 0.3848 – 27 0.3375 338 0.3798 130 0.4088 56 0.3889 rs713586 RBJ TT 238 0.3324 23.61 ± 4.13 18 0.4500 146 0.3281 49 0.3082 25 0.3472 TC 340 0.4749 24.08 ± 4.65 18 0.4500 212 0.4764 73 0.4591 37 0.5139 CC 138 0.1927 23.92 ± 3.74 4 0.1000 87 0.1955 37 0.2327 10 0.1389 T 816 0.5698 – 54 0.6750 504 0.5663 171 0.5377 87 0.6042 C 616 0.4302 – 26 0.3250 386 0.4337 147 0.4623 57 0.3958 rs887912 FANCL GG 437 0.6103 23.96 ± 4.47 27 0.6750 270 0.6067 95 0.5975 45 0.6250 GA 238 0.3324 23.68 ± 4.19 12 0.3000 152 0.3416 50 0.3145 24 0.3333 AA 41 0.0573 24.11 ± 3.30 1 0.0250 23 0.0517 14 0.0880 3 0.0417 G 1112 0.7765 – 66 0.8250 692 0.7775 240 0.7547 114 0.7917 A 320 0.2235 – 14 0.1750 198 0.2225 78 0.2453 30 0.2083 rs2241423 MAP2K5 GG 474 0.6620 23.81 ± 4.11 27 0.6750 288 0.6471 115 0.7233 44 0.6111 GA 213 0.2975 23.93 ± 4.65 11 0.2750 141 0.3169 37 0.2327 24 0.3333 AA 29 0.0405 24.72 ± 5.17 2 0.0500 16 0.0360 7 0.0440 4 0.0556 G 1161 0.8108 – 65 0.8125 717 0.8056 267 0.8396 112 0.7778 A 271 0.1892 – 15 0.1875 173 0.1944 51 0.1604 32 0.2222 rs12444979 GPRC5B CC 524 0.7318 23.99 ± 4.36 29 0.7250 320 0.7191 118 0.7421 57 0.7917 CT 175 0.2444 23.56 ± 4.25 11 0.2750 114 0.2562 37 0.2327 13 0.1805 TT 17 0.0238 23.96 ± 3.79 – – 11 0.0247 4 0.0252 2 0.0278 C 1223 0.8541 – 69 0.8625 754 0.8472 273 0.8585 127 0.8819 T 209 0.1459 – 11 0.1375 136 0.1528 45 0.1415 17 0.1181 The frequencies of alleles and genotypes for single nucleotide polymorphisms (SNPs) rs1514175 TNNI3K , rs713586 RBJ, rs887912 FANCL , rs2241423 MAP2K5 , rs12444979 GPRC5B in the sample of Russian women.

From 2009 to 2013, women referred to the Perinatal Centre of the Belgorod Regional Clinical Hospital of St. Joasaph were enrolled. The participants were unrelated Russian women born in Central Russia [ 11 ]. Some exclusion criteria were adopted: benign tumors and hyperplastic disorders of the reproductive organs (endometriosis, leiomyoma, and endometrial hyperplasia), malignant tumors of a small pelvis and breast, severe autoimmune diseases, chronic severe diseases of the vital organs (heart, respiratory or renal failure). A total of 716 women met the criteria. This study was approved by the Regional Ethics Committee of Belgorod State University and informed consents were obtained from all participants. The anthropometric characteristics were obtained by standard methods [ 12 ]: a portable stadiometer was used for measurement of height; weight was measured in an upright position, using a calibrated balance beam scale. 5 groups were formed according to BMI: total sample set, sample set with the underweight (BMI30.00). Whole blood specimens were collected from each participant using a plastic tubes (Vacutainer®) containing 0.5 M EDTA solution (рН = 8.0) and genomic DNA was isolated from peripheral blood leukocytes using the standard phenol-chloroform method. The isolated DNA was stored at −80°С. Five SNPs in five genes, rs1514175 TNNI3K , rs713586 RBJ, rs887912 FANCL , rs2241423 MAP2K5 , and rs12444979 GPRC5B were selected for the analysis according to the following criteria [ 13 ]: 1) Previously reported genome-wide and candidate genes associations with body mass index (BMI) and obesity, 2) Regulatory potential (regSNP), 3) Effect on gene expression (eSNP), and 4) Tag value (tagSNP) and 5) MAF > 5%. The selected loci were associated with BMI in previously published genome-wide and candidate gene association studies ( Table 2 ) and have functional significance: all SNPs appear to have a significant regulatory potential ( Table 3 ) (determined using the online tools HaploReg, v4.1 update November 05, 2015, https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php ) and 4 SNPs to influence gene expression level ( Table 4 ) (determined using the GTExportal data, http://www.gtexportal.org/ ). Table 2 The literature data about associations of the studied polymorphisms with body mass index and obesity. Table 2 Chr (1) SNP (2 Gene/Region Phenotype Association (significance) (associated allele/genotype) Reference 1 rs1514175 TNNI3K Body mass index 0.07 kg/m 2 (p  =  8 x10 −14 ) (А) [ 1 ] Body mass index 0.06 unit (p  =  3 x10 −11 ) (А) [ 3 ] Body mass index 0.20 kg/m 2 (p = 7.7 × 10 −4 ) (A) [ 4 ] 2 rs713586 RBJ Body mass index 0.14 kg/m 2 (p  =  6 x10 −22 ) (С) [ 1 ] 2 rs887912 FANCL Body mass index 0.1 kg/m 2 (p  =  2 x10 −12 ) (T) [ 1 ] Obesity (class I) OR  =  1.07 (p  =  1 x10 −10 ) (T) [ 2 ] Obesity (class II) OR  =  1.1 (p  =  6 x10 −9 ) (T) [ 2 ] 15 rs2241423 MAP2K5 Body mass index 0.13 kg/m 2 (p  =  1 x10 −18 ) (G) Obesity OR = 0.79 (p = 0.029) (A) [ 1 ] Body mass index −0.092 unit (p = 0.028) (A) [ 5 ] Children obesity (p < 0.005) [ 5 ] Obesity OR = 1.34 (0.001) (G) [ 6 ] Adulthood body mass index (p < 0.05) [ 7 ] Body mass index 0.11 kg/m 2 (p = 0.028) (G) [ 8 ] 16 rs12444979 GPRC5B Body mass index 0.17 kg/m 2 (p  =  3 x10 −21 ) (C) [ 1 ] Body mass index (p < 0.05) [ 9 ] Body mass index (EA) (p = 0.014) [ 10 ] Body fat mass (EA) (p = 0.002) [ 10 ] Note: The data from the GWAS are shown in bold. Table 3 Regulatory effects of the 5 SNPs of the TNNI3K, RBJ, FANCL, MAP2K5, and GPRC5B genes (HaploReg, v4.1, update November 05, 2015) ( https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php ). Table 3 chr pos (hg38) variant Reference allele Alternative allele AFR AMR ASN EUR SiPhy Promoter Enhancer DNAse Proteins Motifs NHGRI/EBI GRASP QTL Selected eQTL GENCODE dbSNP freq freq freq freq cons histone marks histone marks bound changed GWAS hits hits hits genes func annot 1 74525960 rs1514175 A G 0.31 0.42 0.2 0.56 ESC, ESDR, IPSC COMP1,ERalpha-a 2 hits 2 hits FPGT-TNNI3K intronic 2 24935139 rs713586 T C 0.9 0.43 0.46 0.46 Pbx3,SP2,TATA 1 hit 3 hits 34 hits 8.5kb 3′ of DNAJC27 2 59075742 rs887912 T C 0.94 0.83 1 0.73 Hoxa5,Znf143 3 hits 12kb 3′ of AC007092.1 15 67794500 rs2241423 G A 0.4 0.43 0.6 0.23 IPSC 1 hit 1 hit 16 hits MAP2K5 intronic 16 19922278 rs12444979 C T 0.09 0.06 0 0.12 LBP-1 1 hit 70 hits 32kb 3′ of AC134300.1 Table 4 The cis -eQTL values of the 5 SNPs of the TNNI3K, RBJ, FANCL, MAP2K5, and GPRC5B genes (according to Genotype-Tissue Expression (GTEx) ( http://www.gtexportal.org/ )). Table 4 chr SNP Gene Gene expression Reference allele Alternative allele Effect Size (β) P -Value Tissue 1 rs1514175 TNNI3K LRRIQ3 A G 0.25 0.0000045 Thyroid 2 rs713586 RBJ ADCY3 T C 0.31 0.00000018 Skin - Sun Exposed (Lower leg) rs713586 RBJ CENPO T C 0.71 2.9E-38 Whole Blood rs713586 RBJ ADCY3 T C 0.51 5.3E-22 Whole Blood rs713586 RBJ ADCY3 T C −0.23 0.0000000000000063 Nerve - Tibial rs713586 RBJ CENPO T C 0.28 0.00000000000031 Artery - Tibial rs713586 RBJ DNAJC27 T C −0.2 0.00000000012 Nerve - Tibial rs713586 RBJ DNAJC27-AS1 T C 0.29 0.0000000003 Whole Blood rs713586 RBJ DNAJC27-AS1 T C −0.27 0.0000000014 Esophagus - Muscularis rs713586 RBJ CENPO T C −0.39 0.0000000042 Brain - Cerebellum rs713586 RBJ ADCY3 T C 0.23 0.0000000091 Artery - Tibial rs713586 RBJ ADCY3 T C 0.18 0.000000014 Adipose - Subcutaneous rs713586 RBJ CENPO T C −0.41 0.00000015 Cells - EBV-transformed lymphocytes rs713586 RBJ ADCY3 T C 0.23 0.00000024 Lung rs713586 RBJ ADCY3 T C 0.18 0.0000006 Adipose - Visceral (Omentum) rs713586 RBJ CENPO T C −0.15 0.00000079 Skin - Sun Exposed (Lower leg) rs713586 RBJ CENPO T C 0.18 0.0000011 Adipose - Subcutaneous rs713586 RBJ DNAJC27-AS1 T C 0.23 0.0000015 Adipose - Visceral (Omentum) rs713586 RBJ ADCY3 T C −0.33 0.0000026 Pituitary rs713586 RBJ DNAJC27-AS1 T C −0.14 0.000004 Skin - Not Sun Exposed (Suprapubic) rs713586 RBJ ADCY3 T C −0.15 0.000016 Nerve - Tibial rs713586 RBJ EFR3B T C 0.19 0.000031 Lung rs713586 RBJ POMC T C −0.21 0.000031 Heart - Atrial Appendage 15 rs2241423 MAP2K5 MAP2K5 G A −0.32 4.1E-19 Artery - Tibial rs2241423 MAP2K5 MAP2K5 G A −0.4 0.0000000000000029 Heart - Atrial Appendage rs2241423 MAP2K5 MAP2K5 G A −0.32 0.000000000000012 Adipose - Subcutaneous rs2241423 MAP2K5 MAP2K5 G A −0.27 0.0000000000001 Thyroid rs2241423 MAP2K5 SKOR1 G A −0.3 0.0000000000019 Lung rs2241423 MAP2K5 SKOR1 G A −0.32 0.0000000000035 Thyroid rs2241423 MAP2K5 SKOR1 G A −0.3 0.000000000014 Muscle - Skeletal rs2241423 MAP2K5 MAP2K5 G A −0.26 0.000000000015 Whole Blood rs2241423 MAP2K5 SKOR1 G A −0.4 0.000000000073 Heart - Left Ventricle rs2241423 MAP2K5 SKOR1 G A −0.29 0.00000000021 Adipose - Subcutaneous rs2241423 MAP2K5 SKOR1 G A −0.35 0.00000000037 Adipose - Visceral (Omentum) rs2241423 MAP2K5 MAP2K5 G A −0.28 0.00000000092 Esophagus - Muscularis rs2241423 MAP2K5 SKOR1 G A −0.26 0.0000000014 Artery - Tibial rs2241423 MAP2K5 SKOR1 G A −0.23 0.0000000062 Skin - Sun Exposed (Lower leg) rs2241423 MAP2K5 MAP2K5 G A −0.22 0.0000000094 Lung rs2241423 MAP2K5 MAP2K5 G A −0.29 0.000000011 Artery - Aorta rs2241423 MAP2K5 SKOR1 G A −0.25 0.000000019 Skin - Not Sun Exposed (Suprapubic) rs2241423 MAP2K5 MAP2K5 G A −0.27 0.000000054 Nerve - Tibial rs2241423 MAP2K5 SKOR1 G A −0.2 0.000000095 Nerve - Tibial rs2241423 MAP2K5 SKOR1 G A −0.32 0.00000011 Artery - Aorta rs2241423 MAP2K5 MAP2K5 G A −0.27 0.00000012 Adipose - Visceral (Omentum) rs2241423 MAP2K5 SKOR1 G A −0.48 0.00000013 Pituitary rs2241423 MAP2K5 SKOR1 G A −0.3 0.00000013 Breast - Mammary Tissue rs2241423 MAP2K5 SKOR1 G A −0.24 0.00000018 Esophagus - Muscularis rs2241423 MAP2K5 MAP2K5 G A −0.25 0.00000019 Breast - Mammary Tissue rs2241423 MAP2K5 MAP2K5 G A −0.23 0.0000009 Heart - Left Ventricle rs2241423 MAP2K5 SKOR1 G A −0.29 0.0000063 Esophagus - Gastroesophageal Junction rs2241423 MAP2K5 SKOR1 G A −0.51 0.000011 Ovary rs2241423 MAP2K5 SKOR1 G A −0.25 0.000012 Colon - Sigmoid rs2241423 MAP2K5 MAP2K5 G A −0.27 0.000013 Esophagus - Gastroesophageal Junction rs2241423 MAP2K5 SKOR1 G A −0.2 0.000016 Colon - Transverse rs2241423 MAP2K5 MAP2K5 G A −0.38 0.000017 Pituitary rs2241423 MAP2K5 RP11-34F13.2 G A −0.29 0.00004 Thyroid 16 rs12444979 GPRC5B KNOP1 C T 0.64 0.00000000000037 Adipose - Subcutaneous rs12444979 GPRC5B KNOP1 C T 0.81 0.00000000000000049 Adipose - Visceral (Omentum) rs12444979 GPRC5B KNOP1 C T 0.66 0.00000000012 Adrenal Gland rs12444979 GPRC5B KNOP1 C T 0.78 0.000000000000000043 Artery - Aorta rs12444979 GPRC5B KNOP1 C T 0.67 0.0000000033 Artery - Coronary rs12444979 GPRC5B KNOP1 C T 0.43 0.0000026 Artery - Tibial rs12444979 GPRC5B KNOP1 C T 0.77 0.0000067 Brain - Cerebellum rs12444979 GPRC5B KNOP1 C T 0.89 0.0000000056 Brain - Hypothalamus rs12444979 GPRC5B KNOP1 C T 0.82 0.0000009 Brain - Nucleus accumbens (basal ganglia) rs12444979 GPRC5B KNOP1 C T 0.81 0.00000000000071 Breast - Mammary Tissue rs12444979 GPRC5B KNOP1 C T 0.73 0.0000015 Cells - EBV-transformed lymphocytes rs12444979 GPRC5B KNOP1 C T 0.69 0.000000062 Colon - Sigmoid rs12444979 GPRC5B KNOP1 C T 0.51 0.0000000005 Colon - Transverse rs12444979 GPRC5B KNOP1 C T 0.89 0.00000000000000071 Esophagus - Gastroesophageal Junction rs12444979 GPRC5B KNOP1 C T 0.58 0.00000000000000021 Esophagus - Mucosa rs12444979 GPRC5B KNOP1 C T 0.75 1.6E-19 Esophagus - Muscularis rs12444979 GPRC5B KNOP1 C T 0.73 0.000000005 Heart - Atrial Appendage rs12444979 GPRC5B KNOP1 C T 0.56 0.00000035 Heart - Left Ventricle rs12444979 GPRC5B KNOP1 C T 0.65 0.00000000000000011 Lung rs12444979 GPRC5B KNOP1 C T 0.73 2.00E-20 Muscle - Skeletal rs12444979 GPRC5B KNOP1 C T 0.91 0.00000000000000013 Nerve - Tibial rs12444979 GPRC5B KNOP1 C T 1 0.000000042 Ovary rs12444979 GPRC5B KNOP1 C T 1 0.000000000000029 Pancreas rs12444979 GPRC5B KNOP1 C T 0.92 0.000000000000016 Skin - Not Sun Exposed (Suprapubic) rs12444979 GPRC5B KNOP1 C T 0.79 4.1E-21 Skin - Sun Exposed (Lower leg) rs12444979 GPRC5B KNOP1 C T 0.95 0.000000059 Spleen rs12444979 GPRC5B KNOP1 C T 0.67 0.000000000000019 Stomach rs12444979 GPRC5B KNOP1 C T 0.55 0.000000000058 Testis rs12444979 GPRC5B KNOP1 C T 0.58 0.000000000006 Thyroid rs12444979 GPRC5B KNOP1 C T 0.77 0.0000015 Vagina rs12444979 GPRC5B KNOP1 C T 0.35 0.000011 Whole Blood rs12444979 GPRC5B GPRC5B C T −0.25 0.000046 Adipose - Subcutaneous The literature data about associations of the studied polymorphisms with body mass index and obesity. Note: The data from the GWAS are shown in bold. Regulatory effects of the 5 SNPs of the TNNI3K, RBJ, FANCL, MAP2K5, and GPRC5B genes (HaploReg, v4.1, update November 05, 2015) ( https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php ). The cis -eQTL values of the 5 SNPs of the TNNI3K, RBJ, FANCL, MAP2K5, and GPRC5B genes (according to Genotype-Tissue Expression (GTEx) ( http://www.gtexportal.org/ )). DNA samples were genotyped using the Sequenom MassARRAY® iPLEX platform. The procedure for DNA sample preparation and data quality control are described elsewhere [ 12 ]. All polymorphisms were checked for their correspondence to the Hardy-Weinberg equilibrium (HWE) using the chi-square test. Differences in allele and genotype frequencies between the groups of underweight (BMI30.00) women were determined using the Kruskall-Wallis test.