The Logistic Regression Model for Gene–Environment Interactions Using Both Case‐Parent Trios and Unrelated Case–Controls

One of the greatest challenges in genetic studies is the determination of gene–environment interactions due to underlying complications and inadequate statistical power. With the increased sample size gained by using case‐parent trios and unrelated cases and controls, the performance may be much improved. Focusing on a dichotomous trait, a two‐stage approach was previously proposed to deal with gene–environment interaction when utilizing mixed study samples. Theoretically, the two‐stage association analysis uses likelihood functions such that the computational algorithms may not converge in the maximum likelihood estimation with small study samples. In an effort to avoid such convergence issues, we propose a logistic regression framework model, based on the combined haplotype relative risk (CHRR) method, which intuitively pools the case‐parent trios and unrelated subjects in a two by two table. A positive feature of the logistic regression model is the effortless adjustment for either discrete or continuous covariates. According to computer simulations, under the circumstances in which the two‐stage test converges in larger sample sizes, we discovered that the performances of the two tests were quite similar; the two‐stage test is more powerful under the dominant and additive disease models, but the extended CHRR is more powerful under the recessive disease model.     

Association between the TNFα‐308 A/G polymorphism and the onset‐age of Alzheimer disease

Local inflammatory processes associated with amyloid plaques would contribute to the progression of late‐onset Alzheimer disease (LOAD). Tumor necrosis factors α (TNFα) and β (LTα) are inflammatory cytokines involved in the local immune response occurring in the central nervous system of LOAD patients. Genetic variation at these genes could contribute to the risk of developing AD or influence the age at the onset of the disease. We genotyped 315 LOAD patients and 400 healthy controls for DNA‐polymorphisms in the genes encoding TNFα (‐308 G/A, ‐238G/A) and LTα (Asn26Thr). Carriers of ‐308A showed a mean age at onset 3 years younger than noncarriers of this allele (P = 0.019). Our data suggest an effect of the TNFα‐308 polymorphism on the age at onset of late AD. This represents additional evidence of the importance of genetic variation at the proinflammatory components in the origin and progression of this common neurodegenerative disease. © 2002 Wiley‐Liss, Inc.     

Linkage and Association Study of Late‐Onset Alzheimer Disease Families Linked to 9p21.3

A chromosomal locus for late‐onset Alzheimer disease (LOAD) has previously been mapped to 9p21.3. The most significant results were reported in a sample of autopsy‐confirmed families. Linkage to this locus has been independently confirmed in AD families from a consanguineous Israeli‐Arab community. In the present study we analyzed an expanded clinical sample of 674 late‐onset AD families, independently ascertained by three different consortia. Sample subsets were stratified by site and autopsy‐confirmation. Linkage analysis of a dense array of SNPs across the chromosomal locus revealed the most significant results in the 166 autopsy‐confirmed families of the NIMH sample. Peak HLOD scores of 4.95 at D9S741 and 2.81 at the nearby SNP rs2772677 were obtained in a dominant model. The linked region included the cyclin‐dependent kinase inhibitor 2A gene (CDKN2A), which has been suggested as an AD candidate gene. By re‐sequencing all exons in the vicinity of CDKN2A in 48 AD cases, we identified and genotyped four novel SNPs, including a non‐synonymous, a synonymous, and two variations located in untranslated RNA sequences. Family‐based allelic and genotypic association analysis yielded significant results in CDKN2A (rs11515: PDT p = 0.003, genotype‐PDT p = 0.014). We conclude that CDKN2A is a promising new candidate gene potentially contributing to AD susceptibility on chromosome 9p.     

Probability that a Two‐Stage Genome‐Wide Association Study will Detect a Disease‐Associated SNP and Implications for Multistage Designs

Large two‐stage genome‐wide association studies (GWASs) have been shown to reduce required genotyping with little loss of power, compared to a one‐stage design, provided a substantial fraction of cases and controls, π_sample , is included in stage 1. However, a number of recent GWASs have used π_sample < 0.2 . Moreover, standard power calculations are not applicable because SNPs are selected in stage 1 by ranking their p‐values, rather than comparing each SNP's statistic to a fixed critical value. We define the detection probability (DP) of a two‐stage design as the probability that a given disease‐associated SNP will have a p‐value among the lowest ranks of p‐values at stage 1, and, among those SNPs selected at stage 1, at stage 2. For 8000 cases and 8000 controls available for study and for odds ratios per allele in the range 1.1‐1.3, we show that DP is substantially reduced for designs with π_sample≤ 0.25 , and that DP cannot be appreciably increased by analyzing the stage 1 and stage 2 data jointly. These results suggest that multistage designs with small first stages (e.g. π_sample≤ 0.25 ) should be avoided, and that additional genotyping in earlier studies with small first stages will yield previously unselected disease‐associated SNPs.     

Association of rs10490924 in ARMS2/HTRA1 with age‐related macular degeneration in the Pakistani population

Age‐related macular degeneration (AMD) is a disease of the elderly in which central vision is lost because of degenerative changes of the macula. The current study investigated the association of single‐nucleotide polymorphisms (SNPs) with AMD in the Pakistani population. Four SNPs were analyzed in this study: rs1061170 in the CFH, rs429608 near CFB, rs2230199 in the C3, and rs10490924 in ARMS2/HTRA1. This case‐control association study was conducted on 300 AMD patients (125 wet AMD and 175 dry AMD) and 200 unaffected age‐ and gender‐matched control individuals. The association of the SNP genotypes and allele frequency distributions were compared between patients and healthy controls, keeping age, gender, and smoking status as covariates. A significant genotype and variant allele association was found of rs10490924 in ARMS2/HTRA1 with wet AMD, while the SNPs in CFH, CFB, and C3 were not associated with AMD in the current Pakistani cohort. The lack of association of CFH, CFB, and C3 may be attributed to limited sample size. This study demonstrates that genetic causative factors of AMD differ among populations and supports the need for genetic association studies among cohorts from various populations to increase our global understanding of the disease pathogenesis.     

Association of Nod‐like receptor protein‐1 (rs2670660) and Toll‐like receptor‐4 (rs4986790) with non‐segmental vitiligo: A case–control study in South Indian population

Non‐segmental vitiligo (NSV) is an autoimmune skin disease. Genetics plays a predominant part in disease pathogenesis. Nucleotide‐binding and oligomerization domain (NOD)‐like receptors and pyrin‐containing protein (NLRP) and Toll‐like receptors (TLR) are pattern recognition receptors in mediating innate immunity. They participate in presenting pathogens and mediating the immune responses. NLRP and TLRs are involved in mediating immune response in various dermatological diseases. Understanding the influence of genetic polymorphisms of NLRP and TLRs associated with immune homeostasis might help us to understand the complex etiopathogenesis of NSV. Thus, we aimed to study the association of NLRP‐1 (rs2670660) and TLR‐4 (rs4986790) and the synergistic effects on disease spectrum, disease activity of NSV in South Indian population. This research was designed as a case–control genetic study with 264 patients and 264 controls. Genotyping of NLRP‐1 (rs2670660) and TLR‐4 (rs4986790) was performed by Taqman 5’ allele discrimination assay and ARMS‐PCR. Plasma levels of proteins were measured by enzyme‐linked immunosorbent assay (ELISA). A statistically significant difference was observed with the frequency of homozygous GG genotype of NLRP‐1 (rs2670660) (17.8% in cases vs. 5.3% in controls) (p < 0.0001; OR‐3.73; 95% CI‐1.94–7.14). Allele G was significantly frequent in 38% of the cases than in controls with 30% (p = 0.004; OR‐1.46; 95% CI‐1.13–1.89). Plasma NLRP‐1 level was significantly higher in patients compared to controls (p < 0.05). Amongst cases, the plasma NLRP‐1 levels did not show any difference with respect to their genotypes (p > 0.05). In TLR‐4 (rs4986790), no significant difference in the frequency of genotypes and allele between cases and controls (p = 0.80) was observed; nevertheless, plasma TLR‐4 was analogous between cases and controls (p > 0.05). Influence of genotype on plasma TLR‐4 showed no significant difference in TLR‐4 levels between GG and ancestral genotype AA, whilst heterozygous AG genotype showed a significant increase of TLR‐4 compared to AA and GG (p = 0.02) amongst NSV cases. The obtained results suggest that NLRP‐1 (rs2670660), and not TLR‐4 ((rs4986790), is associated with increased risk of NSV in South Indian population.     

IFN‐γ +874T/A polymorphism increases susceptibility to post‐traumatic osteomyelitis

Immunological inflammatory reaction is one of the key links in the occurrence and development of post‐traumatic osteomyelitis after microbial invasion. Growing evidence suggests complex interactions between IFN‐γ and bone remodelling cells. However, potential association of IFN‐γ gene polymorphism with susceptibility to post‐traumatic osteomyelitis remains unclear. This study aimed to investigate the potential link between IFN‐γ +874T/A polymorphism and risk of developing post‐traumatic osteomyelitis. A total of 189 patients with post‐traumatic osteomyelitis and 200 healthy controls were enrolled for genotyping using the SNaPshot genotyping method. Statistically significant associations were found between the gene polymorphism and the risk of post‐traumatic osteomyelitis by dominant model (AA + AT vs. TT, OR = 1.820, p = .017) and heterozygous model (AT vs. TT, OR = 1.781, p = .029). Moreover, the frequency of mutant allele A was significantly higher in the patients than that in the healthy controls (15.07% vs. 9.25%, OR = 1.742, p = .013). IFN‐γ +874T/A polymorphism may contribute to the increased susceptibility to post‐traumatic osteomyelitis.     

The Association between the Polymorphisms in a Sodium Channel Gene SCN7A and Essential Hypertension: A Case‐Control Study in the Northern Han Chinese

Na_x, an α‐subunit of the sodium channel encoded by the SCN7A gene, has been deemed to be a sensor of the concentration of sodium in the brain and may be involved in salt intake behavior. We inferred that Na_x/SCN7A may participate in the regulation of blood pressure and the pathogenesis of essential hypertension (EH). The present case‐control study involving 615 hypertensives and 617 normotensives was performed to investigate the association between SCN7A polymorphisms and EH in the Northern Han Chinese population. The three common single nucleotide polymorphisms (SNPs) (rs3791251, rs6738031, rs7565062) in the exons of SCN7A were genotyped with the TaqMan assay. Significant association between SNP rs7565062 and EH was found under the addictive and dominant genetic models (P = 0.024, OR = 1.283, 95%CI [1.033–1.592]; P = 0.013, OR = 1.203, 95%CI [1.040–1.392]; respectively). The three SNPs were in close pair‐wise linkage disequilibrium with each other and the haplotype analyses indicated that haplotype G–A–T was significantly associated with increased risk of EH (P = 0.023, OR = 1.290). In conclusion, our data showed that SNP rs7565062 of SCN7A was significantly associated with EH and the allele T of rs7565062 or the related haplotype G–A–T will be a genetic risk factor for EH in the Northern Han Chinese population.     

Exploring the Major Sources and Extent of Heterogeneity in a Genome‐Wide Association Meta‐Analysis

Genome‐wide association (GWA) meta‐analysis has become a popular approach for discovering genetic variants responsible for complex diseases. The between‐study heterogeneity effect is a severe issue that may complicate the interpretation of results. Aiming to improve the interpretation of meta‐analysis results, we empirically explored the extent and source of heterogeneity effect. We analyzed a previously reported GWA meta‐analysis of obesity, in which over 21,000 subjects from seven individual samples were meta‐analyzed. We first evaluated the extent and distribution of heterogeneity across the entire genome. We then studied the effects of several potentially confounding factors, including age, ethnicity, gender composition, study type, and genotype imputation on heterogeneity with a random‐effects meta‐regression model. Of the total 4,325,550 SNPs being tested, heterogeneity was moderate to very large for 25.4% of the total SNPs. Heterogeneity was more severe in SNPs with stronger association signals. Ethnicity, average age, and genotype imputation accuracy had significant effects on the heterogeneity. Exploring the effects of ethnicity can provide clues to the potential ethnic‐specific effects for two loci known to affect obesity, MC4R, and MTCH2. Our analysis can help to clarify understanding of the obesity mechanism and may provide guidance for an effective design of future GWA meta‐analysis.     

Genome‐Wide Association Study Confirms SNPs in SNCA and the MAPT Region as Common Risk Factors for Parkinson Disease

Parkinson disease (PD) is a chronic neurodegenerative disorder with a cumulative prevalence of greater than one per thousand. To date three independent genome‐wide association studies (GWAS) have investigated the genetic susceptibility to PD. These studies implicated several genes as PD risk loci with strong, but not genome‐wide significant, associations. In this study, we combined data from two previously published GWAS of Caucasian subjects with our GWAS of 604 cases and 619 controls for a joint analysis with a combined sample size of 1752 cases and 1745 controls. SNPs in SNCA (rs2736990, p‐value = 6.7 × 10^?8; genome‐wide adjusted p = 0.0109, odds ratio (OR) = 1.29 [95% CI: 1.17–1.42] G vs. A allele, population attributable risk percent (PAR%) = 12%) and the MAPT region (rs11012, p‐value = 5.6 × 10^?8; genome‐wide adjusted p = 0.0079, OR = 0.70 [95% CI: 0.62–0.79] T vs. C allele, PAR%= 8%) were genome‐wide significant. No other SNPs were genome‐wide significant in this analysis. This study confirms that SNCA and the MAPT region are major genes whose common variants are influencing risk of PD.     

Association of with‐no‐lysine kinase 1 and Serine/Threonine kinase 39 gene polymorphisms and haplotypes with essential hypertension in Tibetans

Tibetans have a higher essential hypertension prevalence compared with other ethnics in China. The reason might be due to their unique environmental influence, as well as genetic factor. However, limited studies focus on Tibetan genetics and its association with hypertension. The aim of this study was to investigate the association between With‐No‐Lysine (K) Kinase 1 (WNK1), Serine/Threonine kinase 39(STK39) genes variants and hypertension in the Tibetan population. 204 Tibetan hypertensive patients and 305 normotensive controls were recruited in an epidemiological survey conducted at 2 sites in the Ganzi Tibetan autonomous region. Patients were genotyped for nineteen WNK1 candidate tag single nucleotide polymorphisms (SNPs) and three STK39 SNPs, and haplotype analysis was performed. Results showed that the allele A in rs1468326 was overrepresented in hypertensive patients versus control (53.4% vs 42.9%, P < 0.05). The multivariable‐adjusted odds ratio (OR) for hypertension among CA + AA genotypes carriers was 1.60 (95% CI: 1.02–2.62, P < 0.05), and they also had a higher systolic blood pressure (136.5 ± 28.6 vs 131.7 ± 24.8 mmHg, P < 0.05). However, the TT genotype ratio in rs6749447 was lower in hypertensives (5.4% vs 10.8%, P < 0.05), and the hypertension risk for the TT genotype carriers in rs6749447 decreased after adjustment (OR 0.49, 95% CI 0.19–0.95, P < 0.05). Subjects with haplotype AGACAGGAATCGT showed 1.57 times higher risk of hypertension (95% CI 1.02–2.41, P < 0.05). In conclusion, SNP rs1468326 of WNK1, rs6749447 of STK39, and WNK1 haplotype AGACAGGAATCGT were associated with hypertension in Tibetan individuals. Environ. Mol. Mutagen. 59:151–160, 2018. © 2017 Wiley Periodicals, Inc.     

Family‐based and population study of a functional promoter‐region monoamine oxidase A polymorphism in autism: Possible association with IQ

Although the etiology of autism remains to be elucidated, genetic elements significantly contribute to this disorder, and genes on the X chromosome are of special interest because there is a 4:1 predominance of male probands in autism. In the current study, we therefore examined, using the robust transmission disequilibrium test (TDT), possible preferential transmission of variants of a functional monoamine oxidase A (MAO A) promoter region polymorphism for linkage to autism. In the 49 families examined (33 families with one proband and 15 families with two affected siblings), we did not find preferential transmission of MAO A from 33 heterozygous mothers to affected child (TDT chi‐square = 0.29, NS). Nor was any significant difference in MAO A allele frequency observed between 43 male autism subjects versus a group of 108 non‐autism control subjects (chi‐square = 1.23, P = 0.27, NS). However, a trend was observed for an association between IQ in the probands and the MAO A genotype that just attained significance (F = 3.5, P = 0.046, N = 28) in the small group of autism subjects recruited from families with two affected siblings. © 2002 Wiley‐Liss, Inc.     

Study on the polymorphisms of HLA‐ABCDQB1DRB1 alleles and haplotypes in Hubei Han population of China

The present study aimed to analyse the frequencies of human leukocyte antigen HLA‐ABCDQB1 and HLA‐DRB1 alleles and haplotypes in a subset of 3,732 Han population from Hubei of China. All samples were typed in the HLA‐ABCDQB1 and HLA‐DRB1 loci using the sequence‐based typing method; subsequently, the HLA polymorphisms were analysed. A total of 47 HLA‐A, 89 HLA‐B, 43 HLA‐C, 49 HLA‐DRB1 and 24 HLA‐DQB1 alleles were identified in the Hubei Han population. The top three most frequent alleles in the HLA‐ABCDQB1 and HLA‐DRB1 were A*11:01 (0.2617), A*24:02 (0.1590), A*02:07 (0.1281); B*46:01 (0.1502), B*40:01 (0.1409) and B*58:01 (0.0616); C*01:02 (0.2023), C*07:02 (0.1691) and C*03:04 (0.1175); and DQB1*03:01 (0.2000), DQB1*03:03 (0.1900), DQB1*06:01 (0.1187); DRB1*09:01 (0.1790), DRB1*15:01 (0.1062) and DRB1*12:02 (0.0841), respectively. Meanwhile, the three most frequent two‐loci haplotypes were A*02:07‐C*01:02 (0.0929), B*46:01‐C*01:02 (0.1366) and DQB1*03:03‐DRB1*09:01 (0.1766). The three most frequent three‐loci haplotypes were A*02:07‐B*46:01‐C*01:02 (0.0883), B*46:01‐DQB1*03:03‐DRB1*09:01 (0.0808) and C*01:02‐DQB1*03:03‐DRB1*09:01 (0.0837). The three most frequent four‐loci haplotypes were A*02:07‐B*46:01‐C*01:02‐DQB1*03:03 (0.0494), B*46:01‐DRB1*09:01‐C*01:02‐DQB1*03:03 (0.0729) and A*02:07‐B*46:01‐DQB1*03:03‐DRB1*09:01 (0.0501). The most frequent five‐loci haplotype was A*02:07‐B*46:01‐C*01:02‐DQB1*03:03‐DRB1*09:01 (0.0487). Heat maps and multiple correspondence analysis based on the frequencies of HLA specificity indicated that the Hubei Han population might be described into Southern Chinese populations. Our results lay a certain foundation for future population studies, disease association studies and donor recruitment strategies.     

Association of group‐specific component exon 11 polymorphisms with bronchial asthma in children and adolescents

Several studies have investigated the association of Group‐specific Component (GC) gene, also known as vitamin D‐binding protein (VDBP), and various respiratory disorder susceptibility with conflicting results. In this sense, we aimed to investigate whether rs7041 and rs4588 variants confer susceptibility to bronchial asthma in a sample of an Egyptian population and to elucidate by in silico analysis the structural and functional impact of these variants. Group‐specific Component polymorphisms rs7041 and rs4588 were genotyped in 192 Egyptian children and adolescents (96 with asthma and 96 healthy controls) by TaqMan single nucleotide polymorphism genotyping assay. The rs7041 GG genotype showed a significantly elevated frequency among patients under codominant, dominant, recessive and allelic models where the patient group had greater carriage rate of G allele [OR 2.15, CI 95% (1.32‐3.50; P = 0.002)], while rs4588 CA and AA genotypes were found to be protective genotypes with controls showing a greater carriage rate of A allele [OR 0.52, CI 95% (0.30 ‐ 0.90; P = 0.02)]. Three haplotype allele combinations were identified with frequencies of GC (44.3%), TC (31.3%) and TA (24.5%) in the total study population. GC haplotype was shown to be more frequent in controls, while TC and TA haplotypes were more predominant in the patient group. Only rs7041 variant showed a significant association with family history and pubertal status. In conclusion, both study GC variants could be implicated in childhood bronchial asthma pathogenesis; rs7041 GG genotype and G allele increased asthma risk while rs4588 AA genotype and A allele conferred protection in the study population.     

A population‐based study of hereditary non‐polyposis colorectal cancer: evidence of pathologic and genetic heterogeneity

Hereditary non‐polyposis colorectal cancer (HNPCC) may be the result of Lynch syndrome (LS) caused by mutations in mismatch repair (MMR) genes, a syndrome of unknown etiology called familial colorectal cancer type‐X (FCCTX), or familial serrated neoplasia associated with the colorectal cancer (CRC) somatic BRAF mutation. To determine the cause of HNPCC in the founder population of the island of Newfoundland, we studied 37 families with LS and 29 families without LS who fulfilled the Amsterdam I criteria. In non‐LS, four index CRCs were BRAF mutation positive, one of which was microsatellite instable. Geographic clustering of LS families caused by three different founder mutations in MSH2 was observed. Nine unique MMR mutations in four MMR genes were identified in single families distributed in different geographic isolates. The geographic distribution of non‐LS was similar to LS. The coefficient of relatedness using genotype data was significantly higher for non‐LS than for all CRC. Extensive genealogic investigation failed to connect non‐LS families and in some clusters pathologic CRC heterogeneity was observed. We conclude that non‐LS HNPCC may be a heterogeneous disorder with different pathogenic pathways, and that the geographic distribution is consistent with multiple different mutations in unknown CRC susceptibility gene(s).     

Electrophysiological evidence for early perceptual facilitation and efficient categorization of self‐related stimuli during an Implicit Association Test measuring neuroticism

The Implicit Association Test (IAT) is a widely used latency‐based categorization task that indirectly measures the strength of automatic associations between target and attribute concepts. So far, little is known about the perceptual and cognitive processes underlying personality IATs. Thus, the present study examined event‐related potential indices during the execution of an IAT measuring neuroticism (N = 70). The IAT effect was strongly modulated by the P1 component indicating early facilitation of relevant visual input and by a P3b‐like late positive component reflecting the efficacy of stimulus categorization. Both components covaried, and larger amplitudes led to faster responses. The results suggest a relationship between early perceptual and semantic processes operating at a more automatic, implicit level and later decision‐related categorization of self‐relevant stimuli contributing to the IAT effect.     

Association between symptoms and subtypes of attention‐deficit hyperactivity disorder and sleep problems/disorders

This study aimed to investigate the association between attention‐deficit hyperactivity disorder (ADHD) symptoms and subtypes, and sleep schedules, daytime inadvertent napping, and sleep problems/disorders in children and adolescents with and without ADHD. The sample included 325 patients with ADHD, aged 10–17 years [male: 81.5%; combined type (ADHD‐C): 174; predominantly inattentive type (ADHD‐I): 130; predominantly hyperactive‐impulsive type (ADHD‐HI): 21], and 257 children and adolescents without lifetime ADHD (non‐ADHD). We conducted psychiatric interviews with the participants and their mothers before making the diagnoses of ADHD, other psychiatric disorders, and sleep problems or disorders. We also collected the medication treatment data and parent and teacher reports of ADHD symptoms. Multi‐level models were used for data analyses controlling for sex, age, psychiatric comorbidities, and treatment with methylphenidate. The ADHD‐C and ADHD‐I groups had more daytime inadvertent napping. In general, the three subtypes were associated with increased rates of sleep problems/disorders. Specifically, ADHD‐C rather than ADHD‐I was associated with circadian rhythm problems, sleep‐talking, nightmares (also ADHD‐HI), and ADHD‐I was associated with hypersomnia. The most‐related sleep schedules and problems for inattention and hyperactivity‐impulsivity were earlier bedtime, later rise time, longer nocturnal sleep, more frequent daytime napping, insomnia, sleep terrors, sleep‐talking, snoring, and bruxism across informants. The findings imply that in addition to the dichotomous approach of ADHD and considering the psychiatric comorbid conditions, ADHD subtypes and symptom dimensions need to be considered in clinical practice and in the research regarding the association between ADHD and sleep problems/disorders.     

Genetic polymorphism of human leucocyte antigen and susceptibility to multidrug‐resistant and rifampicin‐resistant tuberculosis in Han Chinese from Hubei Province

We determined the high‐resolution allele and haplotype frequencies at the human leucocyte antigen (HLA)A, B and DRB1 loci in the Han population of Hubei province, the TB endemic area of Central China, with pulmonary tuberculosis (PTB), and established the relationship between HLA‐A, B and DRB1 alleles as well as haplotypes and susceptibility to multidrug‐resistant and rifampicin‐resistant tuberculosis (MDR/RR‐TB). Blood samples were drawn from 174 patients with MDR/RR‐TB and 838 patients with drug‐susceptible PTB in ethnic Han population from Hubei province (central China). Four‐digit allele genotyping of HLA‐ A, B and DRB1 loci was performed using polymerase chain reaction with sequence‐specific oligonucleotide probes (PCR‐ SSOP). The allele and haplotype frequencies of HLA‐A, B and DRB1 were determined and compared between patients with MDR/RR‐TB and patients with drug‐susceptible PTB. Statistical analysis of the generated data indicated no departure from expectation of Hardy–Weinberg equilibrium (HWE) at all loci of the control group. Multivariate analysis identified allele DRB1*08:01 (p < .0001; OR = 174.5, 95% CI 15.3–1987.2) as independent predictor of MDR/RR‐TB, except for old age (p < .0001; OR = 10. 9, 95% CI 7.6–15.8), previous treatment history (p < .0001; OR = 11.0, 95% CI 7.2–16.7) and poor compliance to treatment (p < .0001; OR = 12.9, 95% CI 8.4–20.0). While in the subgroup of new TB cases, DRB1*08:01 (p < .0001; OR = 80.3, 95% CI 7.0–917.1) and older age (p < .0001; OR = 3.9, 95% CI 2.4–6.4) were independent susceptibility factors for primary MDR/RR‐TB. Our results suggest that a combination of clinical and host genetic information about tuberculosis patients may contribute to prediction and early detection of MDR/RR‐TB.