Hypercholesterolemia and a candidate gene within the 12q24 locus

Background

The 12q24 locus entails at least one gene responsible for hypercholesterolemia. Within the 12q24 locus lies the gene of proteasome modulator 9 (PSMD9). PSMD9 is in linkage with type 2 diabetes (T2D), T2D-nephropathy and macrovascular pathology in Italian families and PSMD9 rare mutations contribute to T2D.

Aims

In the present study, we aimed at determining whether the PSMD9 T2D risk single nucleotide polymorphisms (SNPs) IVS3 + nt460 A > G, IVS3 + nt437 T > C and E197G A > G are linked to hypercholesterolemia in 200 T2D Italian families.

Methods

We characterized 200 Italian families for presence and/or absence of hypercholesterolemia characterized by LDL levels ≥ 100 mg/dl in drug-naïve patients and/or presence of a diagnosis of hypercholesterolemia in a patient treated with statin medication. The phenotypes were described as unknown in all cases in which the diagnosis was either unclear or the data were missing. We tested in the 200 Italians families for evidence of linkage of the PSMD9 SNPs with hypercholesterolemia. The non-parametric linkage analysis was performed for the qualitative phenotype by using the Merlin software; the Lod score and correspondent P-value were calculated. For the significant linkage score, 1000 replicates were performed to calculate the empirical P-value.

Results

The PSMD9 gene SNPs studied show linkage to hypercholesterolemia. The results are not due to random chance.

Conclusions

PSMD9 should be tested in all populations reporting linkage to hypercholesterolemia within the chromosome 12q24 locus. The impact of this gene on hypercholesterolemia and contribution to cardio- and cerebrovascular events may be high.     

Confirmation of chromosome 7q11 locus for predisposition to intracranial aneurysm

A significant linkage of intracranial aneurysm (IA) has recently been reported to chromosomal region 7q11 (MLS=3.22) in a genomic search of 85 Japanese nuclear families with at least two affected siblings (104 sib pairs). This region contains the elastin gene (ELN, OMIM 130160), which is a functional candidate gene for IA. We have replicated this finding through linkage analyses in 13 extended pedigrees from Utah, comprising 39 IA cases. We genotyped three markers flanking ELN and performed two-point and multipoint parametric analyses, employing simple dominant and recessive models. Analyses utilizing a recessive affecteds-only model yielded significant confirmation of linkage to the region (best evidence, multipoint TLOD=2.34, at D7S2421, corrected P=0.001). This study is the first to confirm the linkage of the 7q11 locus for IA.     

CHOP T/C and C/T haplotypes contribute to early-onset type 2 diabetes in Italians

Type 2 diabetes (T2D) is characterized by impaired insulin secretion, insulin insensitivity and decreased beta-cell mass. Multiple genes contribute to T2D. The chromosome 12q13.1 region is in linkage to T2D in different populations, including our Italian dataset. CHOP is a candidate gene for the linkage, as it is located in the chromosome 12q13.1 region, and may contribute to T2D by increasing beta-cell apoptosis susceptibility and by impairing insulin sensitivity. Our goal was to identify any potential CHOP gene variants contributing to T2D in our Italian early-onset T2D families, which show linkage to the CHOP region. We directly sequenced the CHOP gene in 28 Italian probands of the linked T2D families and in 115 control subjects. We performed genotype and haplotype association tests with T2D of the identified single nucleotide polymorphisms (SNPs). We performed model-free and parametric association haplotype tests with T2D. We identified three SNPs [5'UTR-c.279T > C, 5'UTR-c.120A > G and + nt30C > T (F10F)] in CHOP. These SNPs are in complete linkage disequilibrium. The genotype association test showed an association trend with T2D of TT (F10F) and AG (-c.120A > G). The haplotype association test provided significant results for the haplotypes T/C (frequency = 0.33) and C/T (frequency = 0.01) (at 5'UTR-c.279T > C and + nt30C > T, respectively) under non-parametric analysis (P-value = 0.0000), recessive model (P-value = 0.0000) and additive model (P-value = 0.0014). Our data show that CHOP described haplotypes T/C and C/T, as an additive and as a homozygous variant, contribute significantly to T2D in our Italian early-onset group. We conclude that the CHOP T/C and C/T haplotype contributes to our T2D linkage signal on chromosome 12q13.1.     

Polymorphism of SLC14A1 encoding human erythrocytic Kidd antigens in the Chinese population

The SLC14A1 gene, which encodes the important Kidd blood group antigens, has not been systematically?analyzed at the molecular level in Chinese individuals. In this study, SLC14A1 genetic polymorphism was examined in Chinese individuals with Jk(a+b-), Jk(a+b+), and Jk(a-b+) expression. The Kidd phenotype was determined for 146 specimens using monoclonal anti-Jk^a and -Jk^b antibodies. From these, 87 specimens were Jk(a-b+), 21 were Jk(a+b-), and 38 were Jk(a+b+). According to the Kidd phenotype results, 20 specimens were randomly selected from each group, i.e., Jk(a-b+), Jk(a+b-), and Jk(a+b+), for the molecular analyses of exons 3 to 11 of the SLC14A1 gene. Novel alleles were detected in the SLC14A1 gene, including IVS3-106A, IVS3-99A, exon3 130G, IVS4-299G, IVS4-293G, IVS4+211C, IVS4 +230C, exon6 499A, exon6 588A, IVS7-68T, IVS9+244G, and IVS10-153T, indicating that the locus harbored significant polymorphism. We also showed that IVS4-299, IVS7-68, and IVS10-153 were novel SNPs absolutely associated with exon 8 nt. 838. The minor allele frequencies were all greater than 10% and all SNPs in the Chinese population showed Vel antigen expression on RBC membranes. We identified 12 SNPs in the SLC14A1 gene in the Chinese population, IVS3-106A, IVS3-99A, exon3 130G, IVS4-299G, IVS4-293G, IVS4+211C, IVS4 +230C, exon6 499A, exon6 588A, IVS7-68T, IVS9+244G, and IVS10-153T. Our results also indicated that three novel SNPs produced Jk^a and Jk^b antigens in Chinese individuals.     

Novel Y‐chromosome polymorphisms in Chinese domestic yak

Y‐chromosome‐specific haplotypes (Y‐haplotypes) constructed using single nucleotide polymorphisms (Y‐SNPs) in the MSY (male‐specific region of the Y‐chromosome) are valuable in population genetic studies. But sequence variants in the yak MSY region have been poorly characterized so far. In this study, we screened a total of 16 Y‐chromosome‐specific gene segments from the ZFY, SRY, UTY, USP9Y, AMELY and OFD1Y genes to identify Y‐SNPs in domestic yaks. Six novel Y‐SNPs distributed in the USP9Y (g.223C>T), UTY19 (g.158A>C and g.169C>T), AMELY2 (g.261C>T), OFD1Y9 (g.165A>G) and SRY4 (g.104G>A) loci, which can define three Y‐haplotypes (YH1, YH2 and YH3) in yaks, were discovered. YH1 was the dominant and presumably most ancient haplotype based on the comparison of UTY19 locus with other bovid species. Interestingly, we found informative UTY19 markers (g.158A>C and g.169C>T) that can effectively distinguish the three yak Y‐haplotypes. The nucleotide diversity was 1.7 × 10^?4 ± 0.3 × 10^?4, indicating rich Y‐chromosome diversity in yaks. We identified two highly divergent lineages (YH1 and YH2 vs. YH3) that share similar frequencies (YH1 +  YH2: 0.82–0.89, YH3: 0.11–0.18) among all three populations. In agreement with previous mtDNA studies, we supported the hypothesis that the two highly divergent lineages (YH1 and YH2 vs. YH3) derived from a single gene pool, which can be explained by the reunion of at least two paternal populations with the divergent lineages already accumulated before domestication. We estimated a divergence time of 408 110 years between the two divergent lineages, which is consistent with the data from mitochondrial DNA in yaks.     

Genetic analysis of diabetic nephropathy on chromosome 18 in African Americans: linkage analysis and dense SNP mapping

Genetic studies in Turkish, Native American, European American, and African American (AA) families have linked chromosome 18q21.1–23 to susceptibility for diabetes-associated nephropathy. In this study, we have carried out fine linkage mapping in the 18q region previously linked to diabetic nephropathy in AAs by genotyping both microsatellite and single nucleotide polymorphisms (SNPs) for linkage analysis in an expanded set of 223 AA families multiplexed for type 2 diabetes associated ESRD (T2DM-ESRD). Several approaches were used to evaluate evidence of linkage with the strongest evidence for linkage in ordered subset analysis with an earlier age of T2DM diagnosis compared to the remaining pedigrees (LOD 3.9 at 90.1 cM, ∆P = 0.0161, NPL P value = 0.00002). Overall, the maximum LODs and LOD-1 intervals vary in magnitude and location depending upon analysis. The linkage mapping was followed up by performing a dense SNP map, genotyping 2,814 SNPs in the refined LOD-1 region in 1,029 AA T2DM-ESRD cases and 1,027 AA controls. Of the top 25 most associated SNPs, 10 resided within genic regions. Two candidate genes stood out: NEDD4L and SERPINB7. SNP rs512099, located in intron 1 of NEDD4L, was associated under a dominant model of inheritance [P value = 0.0006; Odds ratio (95% Confidence Interval) OR (95% CI) = 0.70 (0.57–0.86)]. SNP rs1720843, located in intron 2 of SERPINB7, was associated under a recessive model of inheritance [P value = 0.0017; OR (95% CI) = 0.65 (0.50–0.85)]. Collectively, these results suggest that multiple genes in this region may influence diabetic nephropathy susceptibility in AAs.     

Association of the variants and haplotypes in the DOCK7, PCSK9 and GALNT2 genes and the risk of hyperlipidaemia

Little is known about the association between the single nucleotide polymorphisms (SNPs) and haplotypes of the dedicator of cytokinesis 7 (DOCK7), pro‐protein convertase subtilisin/kexin type 9 (PCSK9) and polypeptide N‐acetylgalactosaminyltransferase 2 (GALNT2) and serum lipid traits in the Chinese populations. This study was to determine the association between nine SNPs in the three genes and their haplotypes and hypercholesterolaemia (HCH)/hypertriglyceridaemia (HTG), and to identify the possible gene–gene interactions among these SNPs. Genotyping was performed in 733 HCH and 540 HTG participants. The haplotype of C‐C‐G‐C‐T‐G‐C‐C‐G [in the order of DOCK7 rs1168013 (G>C), rs10889332 (C>T); PCSK9 rs615563 (G>A), rs7552841 (C>T), rs11206517 (T>G); and GALNT2 rs1997947 (G>A), rs2760537 (C>T), rs4846913 (C>A) and rs11122316 (G>A) SNPs] was associated with increased risk of HCH and HTG. The haplotypes of C‐C‐G‐C‐T‐G‐C‐C‐A and G‐C‐G‐T‐T‐G‐T‐C‐G were associated with a reduced risk of HCH and HTG. The haplotypes of G‐C‐G‐C‐T‐G‐C‐C‐A and G‐C‐G‐C‐T‐G‐T‐C‐G were associated with increased risk of HCH. The haplotypes of C‐T‐G‐C‐T‐G‐C‐C‐G, G‐C‐A‐C‐T‐G‐C‐C‐G and G‐C‐G‐C‐T‐G‐C‐C‐A were associated with an increased risk of HTG. The haplotypes of G‐C‐G‐C‐T‐G‐T‐C‐A and G‐C‐G‐T‐T‐G‐T‐C‐G were associated with a reduced risk of HTG. In addition, possible inter‐locus interactions among the DOCK7, PCSK9 and GALNT2 SNPs were also noted. However, further functional studies of these genes are still required to clarify which SNPs are functional and how these genes actually affect the serum lipid levels.     

Identification of Allelic Heterogeneity at Type-2 Diabetes Loci and Impact on Prediction

Although over 60 single nucleotide polymorphisms (SNPs) have been identified by meta-analysis of genome-wide association studies for type-2 diabetes (T2D) among individuals of European descent, much of the genetic variation remains unexplained. There are likely many more SNPs that contribute to variation in T2D risk, some of which may lie in the regions surrounding established SNPs - a phenomenon often referred to as allelic heterogeneity. Here, we use the summary statistics from the DIAGRAM consortium meta-analysis of T2D genome-wide association studies along with linkage disequilibrium patterns inferred from a large reference sample to identify novel SNPs associated with T2D surrounding each of the previously established risk loci. We then examine the extent to which the use of these additional SNPs improves prediction of T2D risk in an independent validation dataset. Our results suggest that multiple SNPs at each of 3 loci contribute to T2D susceptibility (TCF7L2, CDKN2A/B, and KCNQ1; p<5×10⁻⁸). Using a less stringent threshold (p<5×10⁻⁴), we identify 34 additional loci with multiple associated SNPs. The addition of these SNPs slightly improves T2D prediction compared to the use of only the respective lead SNPs, when assessed using an independent validation cohort. Our findings suggest that some currently established T2D risk loci likely harbor multiple polymorphisms which contribute independently and collectively to T2D risk. This opens a promising avenue for improving prediction of T2D, and for a better understanding of the genetic architecture of T2D.     

Multiple Genes Influence BMI on Chromosome 7q31–34: The NHLBI Family Heart Study

The National Heart, Lung, and Blood Institute Family Heart Study (FHS) genome‐wide linkage scan identified a region of chromosome 7q31–34 with a lod score of 4.9 for BMI at D7S1804 (131.9 Mb). We report the results of linkage and association to BMI in this region for two independent FHS samples. The first sample includes 225 FHS pedigrees with evidence of linkage to 7q31–34, using 1,132 single‐nucleotide polymorphisms (SNPs) and 7 microsatellites. The second represents a case–control sample (318 cases; BMI >25 and 325 controls; BMI <25) derived from unrelated FHS participants who were not part of the genome scan. The latter set was genotyped for 606 SNPs, including 37 SNPs with prior evidence for association in the linked families. Although variance components linkage analysis using only SNPs generated a peak lod score that coincided with the original linkage scan at 131.9 Mb, a conditional linkage analysis showed evidence of a second quantitative trait locus (QTL) near 143 cM influencing BMI. Three SNPs (rs161339, rs12673281, and rs1993068) located near the three genes pleiotrophin (PTN), diacylglycerol (DAG) kinase iota (DGKι), and cholinergic receptor, muscarinic 2 (CHRM2) demonstrated significant association in both linked families (P = 0.0005, 0.002, and 0.03, respectively) and the case–control sample (P = 0.01, 0.0003, and 0.03, respectively), regardless of the genetic model tested. These findings suggest that several genes may be associated with BMI in the 7q31–34 region.     

Pilot study for the characterization of pharmacogenetically relevant CYP2D6, CYP2C19 and ABCB1 gene polymorphisms in the Hungarian population

Polymorphisms of CYP450 metabolizer enzymes and transport proteins play crucial roles in the inter‐individual variability of drug efficiency. The aim of our study was to predict the frequency of functional variants of CYP2D6, CYP2C19 and ABCB1 genes in the Hungarian population. One hundred twelve unrelated healthy subjects donated DNA sample in the study. ABCB1 C3435T and G2677T/A single‐nucleotide polymorphisms (SNPs) were determined by LightCycler polymerase chain reaction. Because only limited amount of data is available on the rare allelic variants of CYP2D6 in the European populations, our study applied an expanded set of CYP2D6 and CYP2C19 alleles by using AmpliChip test. Our results show that the CYP2D6 phenotypes were 1.9% ultra‐rapid metabolizer, 6.5% intermediate metabolizer (IM), 8.3% poor metabolizer (PM) and 83.3% extensive metabolizer (EM), and the CYP2C19 phenotypes were 1.8% PM, 31.2% IM and 67% EM. The prevalence of the commonly observed CYP2D6 and CYP2C19 alleles in our study corresponds with that of other European populations. Nevertheless, our study confirms that extending the CYP2D6 allele set with loss‐of‐function variants such as CYP2D6*7, *9, *41 is worth considering. Frequency of the wild type ABCB1 3435C was 42.8% whereas the prevelance of 2677 G was 50.4%. Although frequency data of G2677T/A SNP in the European area are limited, some discrepancies with other studies were found. Copyright © 2011 John Wiley & Sons, Ltd.     

A gene‐based SNP linkage map for pacific white shrimp,Litopenaeus vannamei

Pacific white shrimp (Litopenaeus vannamei) are of particular economic importance to the global shrimp aquaculture industry. However, limited genomics information is available for the penaeid species. We utilized the limited public information available, mainly single nucleotide polymorphisms (SNPs) and expressed sequence tags, to discover markers for the construction of the first SNP genetic map for Pacific white shrimp. In total, 1344 putative SNPs were discovered, and out of 825 SNPs genotyped, 418 SNP markers from 347 contigs were mapped onto 45 sex‐averaged linkage groups, with approximate coverage of 2071 and 2130 cm for the female and male maps, respectively. The average‐squared correlation coefficient (r²), a measure of linkage disequilibrium, for markers located more than 50 cm apart on the same linkage group, was 0.15. Levels of r² increased with decreasing inter‐marker distance from ～80 cm , and increased more rapidly from ～30 cm . A QTL for shrimp gender was mapped on linkage group 13. Comparative mapping to model organisms, Daphnia pulex and Drosophila melanogaster, revealed extensive rearrangement of genome architecture for L. vannamei, and that L. vannamei was more related to Daphnia pulex. This SNP genetic map lays the foundation for future shrimp genomics studies, especially the identification of genetic markers or regions for economically important traits.     

DFNB48, a new nonsyndromic recessive deafness locus, maps to chromosome 15q23-q25.1

Nonsyndromic deafness locus (DFNB48) segregating as an autosomal recessive trait has been mapped to the long arm of chromosome 15 in bands q23-q25.1 in five large Pakistani families. The deafness phenotype in one of these five families (PKDF245) is linked to D15S1005 with a lod score of 8.6 at =0, and there is a critical linkage interval of approximately 7 cM on the Marshfield human genetic map, bounded by microsatellite markers D15S216 (70.73 cM) and D15S1041 (77.69 cM). MYO9A, NR2E3, BBS4, and TMC3 are among the candidate genes in the DFNB48 region. The identification of another novel nonsyndromic recessive deafness locus demonstrates the high degree of locus heterogeneity for hearing impairment, particularly in the Pakistani population.     

Two closely linked tomato HKT coding genes are positional candidates for the major tomato QTL involved in Na+/K+ homeostasis

The location of major quantitative trait loci (QTL) contributing to stem and leaf [Na⁺] and [K⁺] was previously reported in chromosome 7 using two connected populations of recombinant inbred lines (RILs) of tomato. HKT1;1 and HKT1;2, two tomato Na⁺‐selective class I‐HKT transporters, were found to be closely linked, where the maximum logarithm of odds (LOD) score for these QTLs located. When a chromosome 7 linkage map based on 278 single‐nucleotide polymorphisms (SNPs) was used, the maximum LOD score position was only 35 kb from HKT1;1 and HKT1;2. Their expression patterns and phenotypic effects were further investigated in two near‐isogenic lines (NILs): 157‐14 (double homozygote for the cheesmaniae alleles) and 157‐17 (double homozygote for the lycopersicum alleles). The expression pattern for the HKT1;1 and HKT1;2 alleles was complex, possibly because of differences in their promoter sequences. High salinity had very little effect on root dry and fresh weight and consequently on the plant dry weight of NIL 157‐14 in comparison with 157‐17. A significant difference between NILs was also found for [K⁺] and the [Na⁺]/[K⁺] ratio in leaf and stem but not for [Na⁺] arising a disagreement with the corresponding RIL population. Their association with leaf [Na⁺] and salt tolerance in tomato is also discussed.     

A Rare Variant in the Visfatin Gene (NAMPT/PBEF1) Is Associated With Protection From Obesity

Visfatin was recently reported as a novel adipokine encoded by the NAMPT (PBEF1) gene. This study was aimed at investigation of the possibility that single‐nucleotide polymorphisms (SNPs) in the visfatin gene are associated with either obesity or type 2 diabetes (T2D). A set of eight “tag‐SNPs” were selected and ABI SNPlex assays designed for genotyping purposes. A total of 1,709 severely obese subjects were typed (896 class III obese adults and 813 children) together with 2,367 T2D individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818 from a general population sample. One rare SNP, rs10487818, located in intron 4 of NAMPT was associated with severe obesity, with a minor allele frequency of 1.6% in controls, 0.4% in the class III obese adults and, remarkably, 0% in the severely obese children. A highly significant association was observed for the presence or absence of the rare allele, i.e., (A,A) vs. (A,T + T,T) genotypes, in children (P = 6 × 10^?9) and in adults (P = 8 × 10^?5). No other significant (P < 0.05) association was observed with obesity or T2D for this or any other SNP. No association with BMI or waist‐to‐hip ratio was observed in a general population sample (n = 5,212). This is one of the first rare SNPs shown to be protective against a common polygenic disease and provides further evidence that rare alleles of strong effect can contribute to complex diseases such as severe obesity.     

NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice

Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8⁺ T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D‐mediated immune cell activation, such as tumour‐derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down‐regulate the expression of NKG2D on NK cells and CD8⁺ T cells. Here, we report that surface NKG2D ligand RAE1ε on tumour cells induces CD11b⁺Gr‐1⁺ myeloid‐derived suppressor cell (MDSC) via NKG2D in vitro and in vivo. MDSCs induced by RAE1ε display a robust induction of IL‐10 and arginase, and these MDSCs show greater suppressive activity by inhibiting antigen‐non‐specific CD8⁺ T‐cell proliferation. Consistently, upon adoptive transfer, MDSCs induced by RAE1ε significantly promote CT26 tumour growth in IL‐10‐ and arginase‐dependent manners. RAE1ε moves cytokine balance towards Th2 but not Th1 in vivo. Furthermore, RAE1ε enhances inhibitory function of CT26‐derived MDSCs and promotes IL‐4 rather than IFN‐γ production from CT26‐derived MDSCs through NKG2D in vitro. Our study has demonstrated a novel mechanism for NKG2D ligand⁺ tumour cells escaping from immunosurveillance by facilitating the proliferation and the inhibitory function of MDSCs.     

Association of ADIPOR2 with liver function tests in type 2 diabetic subjects

Objective: Adiponectin protects against liver dysfunction in insulin‐resistant states such as obesity and type 2 diabetes (T2DM), but the role of adiponectin receptors in this disorder is largely unknown. We studied whether common single‐nucleotide polymorphisms (SNPs) in ADIPOR1 and ADIPOR2 are associated with liver function tests (LFTs) in human subjects with various degrees of insulin resistance. Methods and Procedures: Serum alanine (ALT) and aspartate (AST) aminotransferases, homeostasis model assessment of insulin resistance (HOMA‐IR), ?8503 G/A (rs6666089) and +5843 C/T (rs1342387) SNPs in ADIPOR1, ?64,241 T/G (rs1029629) and +33447 C/T (rs1044471) SNPs in ADIPOR2 were assessed in 700 white subjects from a population‐based study. Results: In nondiabetic subjects, the at‐risk alleles for the common ?64,241 T/G and +33447 C/T SNPs in ADIPOR2 were associated with increased circulating adiponectin (P < 0.05 to P < 0.005), but not with LFT. Conversely, in T2DM subjects (who are at risk for liver dysfunction), the same alleles were associated with increased serum ALT and AST (P < 0.05 to P < 0.0001), but not with circulating adiponectin. No significant associations with these parameters were evident for the common ?8503 G/A and +5843 C/T SNPs in ADIPOR1. In a replication study, the ?64,241 T/G and +33447 C/T SNPs in ADIPOR2 were associated with ALT and AST (P < 0.05 to P < 0.0001) in pooled obese and T2DM subjects. Discussion: Common SNPs in ADIPOR2 are associated with LFT in T2DM subjects, which suggests a possible role of this receptor in liver dysfunction associated with insulin resistance.     

Evidence of linkage and association with body fatness and abdominal fat on chromosome 15q26

Objective: In the present study, we undertook a two‐step fine mapping of a 20‐megabase region around a quantitative trait locus previously reported on chromosome 15q26 for abdominal subcutaneous fat (ASF) in an extended sample of 707 subjects from 202 families from the Quebec Family Study. Research Methods and Procedure: First, 19 microsatellites (in addition to the 7 markers initially available on 15q24‐q26; total = 26) were genotyped and tested for linkage with abdominal total fat, abdominal visceral fat, and ASF assessed by computed tomography and with fat mass (FM) using variance component‐based approach on age‐ and sex‐adjusted phenotypes. Second, 16 single nucleotide polymorphisms (SNPs) were genotyped and tested for association using family‐based association tests. Results: After the fine mapping, the peak logarithm of odds ratio (LOD) score (marker D15S1004) increased from 2.79 to 3.26 for ASF and from 3.52 to 4.48 for FM, whereas for abdominal total fat, the peak linkage (marker D15S996) decreased from 2.22 to 1.53. No evidence of linkage was found for abdominal visceral fat. Overall, for genotyped SNPs, three variants located in the putative MCTP2 gene were significantly associated with FM and the three abdominal fat phenotypes (p ≤ 0.05). The major allele and genotype of rs1424695 were associated with higher adiposity values (p < 0.004). The same trend was found for the two other polymorphisms (p < 0.05). None of the other SNPs was associated with adiposity phenotypes. The linkage for FM became non‐significant (LOD = 0.84) after adjustment for the MCTP2 polymorphisms, whereas the one for ASF remained unchanged. Discussion: These results suggest that the MCTP2 gene, located on chromosome 15q26, influences adiposity. Other studies will be needed to investigate the function of the MCTP2 gene and its role in obesity.