To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 ... more To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 (IL-8) promoter region with the diagnosis and age of onset of exudative age-related macular degeneration (AMD) in association with the known genetic risk factors for AMD and tobacco smoking. Medical records, smoking history and angiograms or fundus photographs of 301 patients with exudative AMD, 72 patients with dry AMD and 119 control subjects were analysed retrospectively. The associations of IL-8 rs4073 A→T, CFH rs1061170 T→C, ARMS2 rs10490924 G→T and C3 rs2230199 C→G SNPs with the presence of AMD and with the age of onset of exudative AMD were analysed. Younger age of exudative AMD onset was associated with the homozygous AA genotype of IL-8 rs4073 (p = 0.009, Mann-Whitney U-test), CC genotype of CFH rs1061170 (p = 0.016), TT genotype of ARMS2 rs10490924 (p = 0.001) and with current smoking (p = 0.002). The risk alleles C in CFH rs1061170 (p < 0.0001, Pearson chi-square) and T in ARMS2 rs10490924 (p < 0.0001), as well as smoking (p < 0.0001), were more prevalent in AMD patients compared with controls. No association was found between the IL-8 rs4073 genotype and the presence of AMD. Out of the factors associated with the earlier onset of exudative AMD, only the genotype of IL-8 rs4073 did not appear as a risk factor for AMD in general. IL-8 may have a role in accelerating the development of the choroidal neovascularization in exudative AMD.
It has previously been demonstrated that the advance of the Neolithic Revolution from the Near Ea... more It has previously been demonstrated that the advance of the Neolithic Revolution from the Near East through Europe was decelerated in the northernmost confines of the continent, possibly as a result of space and resource competition with lingering Mesolithic populations. Finland was among the last domains to adopt a farming lifestyle, and is characterized by substructuring in the form of a distinct genetic border dividing the northeastern and southwestern regions of the country. To explore the origins of this divergence, the geographical patterns of mitochondrial and Y-chromosomal haplogroups of Neolithic and Mesolithic ancestry were assessed in Finnish populations. The distribution of these uniparental markers revealed a northeastern bias for hunter-gatherer haplogroups, while haplogroups associated with the farming lifestyle clustered in the southwest. In addition, a correlation could be observed between more ancient mitochondrial haplogroup age and eastern concentration. These results coupled with prior archeological evidence suggest the genetic northeast/southwest division observed in contemporary Finland represents an ancient vestigial border between Mesolithic and Neolithic populations undetectable in most other regions of Europe.
Proceedings. Biological sciences / The Royal Society, Jan 22, 2014
The conventional 'Neolithic package' comprised animals and plants originally domesticated... more The conventional 'Neolithic package' comprised animals and plants originally domesticated in the Near East. As farming spread on a generally northwest trajectory across Europe, early pastoralists would have been faced with the challenge of making farming viable in regions in which the organisms were poorly adapted to providing optimal yields or even surviving. Hence, it has long been debated whether Neolithic economies were ever established at the modern limits of agriculture. Here, we examine food residues in pottery, testing a hypothesis that Neolithic farming was practiced beyond the 60th parallel north. Our findings, based on diagnostic biomarker lipids and δ(13)C values of preserved fatty acids, reveal a transition at ca 2500 BC from the exploitation of aquatic organisms to processing of ruminant products, specifically milk, confirming farming was practiced at high latitudes. Combining this with genetic, environmental and archaeological information, we demonstrate the o...
The incidence of Type 1 diabetes (T1DM) is increasing fast in many populations. The reasons for t... more The incidence of Type 1 diabetes (T1DM) is increasing fast in many populations. The reasons for this are not known, although an increase in the penetrance of the diabetes-associated alleles, through changes in the environment, might be the most plausible mechanism. After the introduction of insulin treatment in 1930s, an increase in the pool of genetically susceptible individuals has been suggested to contribute to the increase in the incidence of Type 1 diabetes. To explore this hypothesis, the authors formulate a simple population genetic model for the incidence change driven by non-Mendelian transmission of a single susceptibility factor, either allele(s) or haplotype(s). A Poisson mixture model is used to model the observed number of cases. Model parameters were estimated by maximizing the log-likelihood function. Based on the Finnish incidence data 1965-1996 the point estimate of the transmission probability was 0.998. Given our current knowledge of the penetrance of the most d...
IEEE International Conference on Bioinformatics and Bioengineering, 2000
We describe a new method for linkage disequilibrium mapping, Haplotype Pattern Mining (HPM). The ... more We describe a new method for linkage disequilibrium mapping, Haplotype Pattern Mining (HPM). The method is based on discovering recurrent patterns, inspired by data mining methods. We define a class of useful haplotype pat- terns in genetic case-control data, and give an algorithm for finding disease-associated haplotypes. The haplotypes are ordered by their strength of association to the pheno- type,
International Journal of Pediatric Otorhinolaryngology, 2012
Otitis media is a multifactorial disease where genetic background may have an important role. For... more Otitis media is a multifactorial disease where genetic background may have an important role. For genome-wide association studies, it is important to understand the degree of heritability. The objective of this study was to estimate the heritability of recurrent acute otitis media and chronic otitis media with effusion. Children operated because of recurrent or chronic otitis media at the Helsinki University Central Hospital, Finland, as well as their families were recruited during 2008-2009. A cohort of 2436 subjects was enrolled consisting of 1279 children and their parents. The study subjects answered a questionnaire concerning their otitis media history and treatment, as well as tobacco exposure, allergy and asthma history. Heritability estimates were calculated for recurrent acute, chronic and any episodes of otitis media using software especially designed for estimating heritability in family cohorts. Altogether 901 subjects suffered from recurrent otitis media and 559 from chronic otitis media with effusion. The heritability estimates in our cohort were 38.5% for recurrent (P=7.3 × 10(-9)), 22.1% for chronic (P=4.6 × 10(-3)) and 47.8% for any otitis media (P=1.5 × 10(-11)). Our results demonstrate a moderately strong and statistically significant genetic component for both recurrent acute otitis media and chronic otitis media with effusion. These results highlight the importance of unraveling the genetic factors for otitis media that are still poorly known.
Not Available Bibtex entry for this abstract Preferred format for this abstract (see Preferences)... more Not Available Bibtex entry for this abstract Preferred format for this abstract (see Preferences) Find Similar Abstracts: Use: Authors Title Return: Query Results Return items starting with number Query Form Database: Astronomy Physics arXiv e-prints
Several variants in the complement cascade genes (complement factor H [CFH], C2, C3, CFB, and Ser... more Several variants in the complement cascade genes (complement factor H [CFH], C2, C3, CFB, and Serping1) have been reported to associate with age-related macular degeneration (AMD). Of these, a member of the complement alternative pathway, CFH, represents the highest risk. As properdin (P) is also an important protein in this pathway, we analysed whether variants in the properdin gene (CFP)
In genetic association analysis a researcher tries to find shared alleles or haplotypes in a grou... more In genetic association analysis a researcher tries to find shared alleles or haplotypes in a group of patients, which would be much rarer in controls. The analysis is based on availability of haplotype data, where phases (which alleles of an individual come from mother, which from father) are known. However this type of data is not always easy to obtain; it is required that either 1) relatives of the probands are genotyped or 2) population based haplotyping algorithms are used. The former is laborious and expensive, the latter is currently restricted to rather simple situations, due to restrictions of the algorithms for resolving haplotypes from a sample of independent genotypes (1). Using phase- unknown genotypes directly for association mapping would have two benefits compared to haplotyping trios: 50% larger sample in terms of alleles can be obtained with equal genotyping cost, and no relatives would have to be recruited. We have previously introduced a non-parametric, data minin...
Autism spectrum disorders (ASD) often show obsessive repetitive symptoms that are characteristic ... more Autism spectrum disorders (ASD) often show obsessive repetitive symptoms that are characteristic to obsessive-compulsive disorder (OCD). Aberrant glutamate function has been suggested to a risk for both ASDs and OCD. Considering the common metabolic pathway and recent results from association studies both in OCD and ASDs, a question, whether there is common molecular background in ASDs and OCD, was raised. Ten single nucleotide polymorphisms (SNPs) at 9p24 and 11p12-p13 containing glutamate transporter genes SLC1A1 and SLC1A2 and their neighboring regions in 175 patients with ASDs and 216 controls of Finnish origin were analyzed using real-time-PCR or direct sequencing. The strongest association was detected with rs1340513 in the JMJD2C gene at 9p24.1 (P=0.007; corrected P=0.011) that is the same SNP associated with infantile autism (P=0.0007) in the autism genome project consortium (2007). No association was detected at 11p12-p13 with ASD. Interestingly, the strongest association in OCD has been found at rs301443 (P=0.000067) residing between SLC1A1 and JMJD2C at 9p24. In summary, our results give evidence for a possible common locus for OCD and ASDs at 9p24. We speculate that the area may represent a special candidate region for obsessive repetitive symptoms in ASDs.
In this study, three single-nucleotide polymorphisms (SNPs) on the lysyl oxidase-like 1 (LOXL1) g... more In this study, three single-nucleotide polymorphisms (SNPs) on the lysyl oxidase-like 1 (LOXL1) gene associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) were investigated in the Finnish population. A case-control study of 59 sporadic patients with XFS, 82 with XFG, 71 with primary open-angle glaucoma (POAG) and 26 individuals without these disorders from the southern Finnish population, and a family study of an extended family with 28 patients with XFS or XFG and 92 unaffected relatives from Kökar islands, Southwestern Finnish archipelago, were conducted. Anonymous blood donors (n=404) were studied as population-based controls. Three SNPs, rs1048661 (R141L), rs3825942 (G153D) and rs2165241, of the LOXL1 gene were genotyped by PCR sequencing. Association and linkage analyses were carried out. In both case-control and family materials, significant association for allele G of rs1048661 (P=2.65 x 10(-5); P=0.0007), allele G of rs3825942 (P=2.24 x 10(-8); P=0.49) and allele T of rs2165241 (P=2.62 x 10(-13); P<0.0001) was found in XFS/XFG. However, linkage was not observed for LOXL1 risk alleles. The corresponding three-locus haplotype GGT increased the risk of XFS/ XFG nearly 15-fold relative to low-risk haplotype GAC (odds ratio (OR): 14.9, P=1.6 x 10(-16)). In conclusion, the earlier reported polymorphisms of the LOXL1 gene showed significant association also in the Finnish population.
Music is listened in all cultures. We hypothesize that willingness to produce and perceive sound ... more Music is listened in all cultures. We hypothesize that willingness to produce and perceive sound and music is social communication that needs musical aptitude. Here, listening to music was surveyed using a web-based questionnaire and musical aptitude using the auditory structuring ability test (Karma Music test) and Carl Seashores tests for pitch and for time. Three highly polymorphic microsatellite markers (RS3, RS1 and AVR) of the arginine vasopressin receptor 1A (AVPR1A) gene, previously associated with social communication and attachment, were genotyped and analyzed in 31 Finnish families (n=437 members) using family-based association analysis. A positive association between the AVPR1A haplotype (RS1 and AVR) and active current listening to music (permuted P=0.0019) was observed. Other AVPR1A haplotype (RS3 and AVR) showed association with lifelong active listening to music (permuted P=0.0022). In addition to AVPR1A, two polymorphisms (5-HTTLPR and variable number of tandem repeat) of human serotonin transporter gene (SLC6A4), a candidate gene for many neuropsychiatric disorders and previously associated with emotional processing, were analyzed. No association between listening to music and the polymorphisms of SLC6A4 were detected. The results suggest that willingness to listen to music is related to neurobiological pathways affecting social affiliation and communication.
To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 ... more To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 (IL-8) promoter region with the diagnosis and age of onset of exudative age-related macular degeneration (AMD) in association with the known genetic risk factors for AMD and tobacco smoking. Medical records, smoking history and angiograms or fundus photographs of 301 patients with exudative AMD, 72 patients with dry AMD and 119 control subjects were analysed retrospectively. The associations of IL-8 rs4073 A→T, CFH rs1061170 T→C, ARMS2 rs10490924 G→T and C3 rs2230199 C→G SNPs with the presence of AMD and with the age of onset of exudative AMD were analysed. Younger age of exudative AMD onset was associated with the homozygous AA genotype of IL-8 rs4073 (p = 0.009, Mann-Whitney U-test), CC genotype of CFH rs1061170 (p = 0.016), TT genotype of ARMS2 rs10490924 (p = 0.001) and with current smoking (p = 0.002). The risk alleles C in CFH rs1061170 (p < 0.0001, Pearson chi-square) and T in ARMS2 rs10490924 (p < 0.0001), as well as smoking (p < 0.0001), were more prevalent in AMD patients compared with controls. No association was found between the IL-8 rs4073 genotype and the presence of AMD. Out of the factors associated with the earlier onset of exudative AMD, only the genotype of IL-8 rs4073 did not appear as a risk factor for AMD in general. IL-8 may have a role in accelerating the development of the choroidal neovascularization in exudative AMD.
It has previously been demonstrated that the advance of the Neolithic Revolution from the Near Ea... more It has previously been demonstrated that the advance of the Neolithic Revolution from the Near East through Europe was decelerated in the northernmost confines of the continent, possibly as a result of space and resource competition with lingering Mesolithic populations. Finland was among the last domains to adopt a farming lifestyle, and is characterized by substructuring in the form of a distinct genetic border dividing the northeastern and southwestern regions of the country. To explore the origins of this divergence, the geographical patterns of mitochondrial and Y-chromosomal haplogroups of Neolithic and Mesolithic ancestry were assessed in Finnish populations. The distribution of these uniparental markers revealed a northeastern bias for hunter-gatherer haplogroups, while haplogroups associated with the farming lifestyle clustered in the southwest. In addition, a correlation could be observed between more ancient mitochondrial haplogroup age and eastern concentration. These results coupled with prior archeological evidence suggest the genetic northeast/southwest division observed in contemporary Finland represents an ancient vestigial border between Mesolithic and Neolithic populations undetectable in most other regions of Europe.
Proceedings. Biological sciences / The Royal Society, Jan 22, 2014
The conventional 'Neolithic package' comprised animals and plants originally domesticated... more The conventional 'Neolithic package' comprised animals and plants originally domesticated in the Near East. As farming spread on a generally northwest trajectory across Europe, early pastoralists would have been faced with the challenge of making farming viable in regions in which the organisms were poorly adapted to providing optimal yields or even surviving. Hence, it has long been debated whether Neolithic economies were ever established at the modern limits of agriculture. Here, we examine food residues in pottery, testing a hypothesis that Neolithic farming was practiced beyond the 60th parallel north. Our findings, based on diagnostic biomarker lipids and δ(13)C values of preserved fatty acids, reveal a transition at ca 2500 BC from the exploitation of aquatic organisms to processing of ruminant products, specifically milk, confirming farming was practiced at high latitudes. Combining this with genetic, environmental and archaeological information, we demonstrate the o...
The incidence of Type 1 diabetes (T1DM) is increasing fast in many populations. The reasons for t... more The incidence of Type 1 diabetes (T1DM) is increasing fast in many populations. The reasons for this are not known, although an increase in the penetrance of the diabetes-associated alleles, through changes in the environment, might be the most plausible mechanism. After the introduction of insulin treatment in 1930s, an increase in the pool of genetically susceptible individuals has been suggested to contribute to the increase in the incidence of Type 1 diabetes. To explore this hypothesis, the authors formulate a simple population genetic model for the incidence change driven by non-Mendelian transmission of a single susceptibility factor, either allele(s) or haplotype(s). A Poisson mixture model is used to model the observed number of cases. Model parameters were estimated by maximizing the log-likelihood function. Based on the Finnish incidence data 1965-1996 the point estimate of the transmission probability was 0.998. Given our current knowledge of the penetrance of the most d...
IEEE International Conference on Bioinformatics and Bioengineering, 2000
We describe a new method for linkage disequilibrium mapping, Haplotype Pattern Mining (HPM). The ... more We describe a new method for linkage disequilibrium mapping, Haplotype Pattern Mining (HPM). The method is based on discovering recurrent patterns, inspired by data mining methods. We define a class of useful haplotype pat- terns in genetic case-control data, and give an algorithm for finding disease-associated haplotypes. The haplotypes are ordered by their strength of association to the pheno- type,
International Journal of Pediatric Otorhinolaryngology, 2012
Otitis media is a multifactorial disease where genetic background may have an important role. For... more Otitis media is a multifactorial disease where genetic background may have an important role. For genome-wide association studies, it is important to understand the degree of heritability. The objective of this study was to estimate the heritability of recurrent acute otitis media and chronic otitis media with effusion. Children operated because of recurrent or chronic otitis media at the Helsinki University Central Hospital, Finland, as well as their families were recruited during 2008-2009. A cohort of 2436 subjects was enrolled consisting of 1279 children and their parents. The study subjects answered a questionnaire concerning their otitis media history and treatment, as well as tobacco exposure, allergy and asthma history. Heritability estimates were calculated for recurrent acute, chronic and any episodes of otitis media using software especially designed for estimating heritability in family cohorts. Altogether 901 subjects suffered from recurrent otitis media and 559 from chronic otitis media with effusion. The heritability estimates in our cohort were 38.5% for recurrent (P=7.3 × 10(-9)), 22.1% for chronic (P=4.6 × 10(-3)) and 47.8% for any otitis media (P=1.5 × 10(-11)). Our results demonstrate a moderately strong and statistically significant genetic component for both recurrent acute otitis media and chronic otitis media with effusion. These results highlight the importance of unraveling the genetic factors for otitis media that are still poorly known.
Not Available Bibtex entry for this abstract Preferred format for this abstract (see Preferences)... more Not Available Bibtex entry for this abstract Preferred format for this abstract (see Preferences) Find Similar Abstracts: Use: Authors Title Return: Query Results Return items starting with number Query Form Database: Astronomy Physics arXiv e-prints
Several variants in the complement cascade genes (complement factor H [CFH], C2, C3, CFB, and Ser... more Several variants in the complement cascade genes (complement factor H [CFH], C2, C3, CFB, and Serping1) have been reported to associate with age-related macular degeneration (AMD). Of these, a member of the complement alternative pathway, CFH, represents the highest risk. As properdin (P) is also an important protein in this pathway, we analysed whether variants in the properdin gene (CFP)
In genetic association analysis a researcher tries to find shared alleles or haplotypes in a grou... more In genetic association analysis a researcher tries to find shared alleles or haplotypes in a group of patients, which would be much rarer in controls. The analysis is based on availability of haplotype data, where phases (which alleles of an individual come from mother, which from father) are known. However this type of data is not always easy to obtain; it is required that either 1) relatives of the probands are genotyped or 2) population based haplotyping algorithms are used. The former is laborious and expensive, the latter is currently restricted to rather simple situations, due to restrictions of the algorithms for resolving haplotypes from a sample of independent genotypes (1). Using phase- unknown genotypes directly for association mapping would have two benefits compared to haplotyping trios: 50% larger sample in terms of alleles can be obtained with equal genotyping cost, and no relatives would have to be recruited. We have previously introduced a non-parametric, data minin...
Autism spectrum disorders (ASD) often show obsessive repetitive symptoms that are characteristic ... more Autism spectrum disorders (ASD) often show obsessive repetitive symptoms that are characteristic to obsessive-compulsive disorder (OCD). Aberrant glutamate function has been suggested to a risk for both ASDs and OCD. Considering the common metabolic pathway and recent results from association studies both in OCD and ASDs, a question, whether there is common molecular background in ASDs and OCD, was raised. Ten single nucleotide polymorphisms (SNPs) at 9p24 and 11p12-p13 containing glutamate transporter genes SLC1A1 and SLC1A2 and their neighboring regions in 175 patients with ASDs and 216 controls of Finnish origin were analyzed using real-time-PCR or direct sequencing. The strongest association was detected with rs1340513 in the JMJD2C gene at 9p24.1 (P=0.007; corrected P=0.011) that is the same SNP associated with infantile autism (P=0.0007) in the autism genome project consortium (2007). No association was detected at 11p12-p13 with ASD. Interestingly, the strongest association in OCD has been found at rs301443 (P=0.000067) residing between SLC1A1 and JMJD2C at 9p24. In summary, our results give evidence for a possible common locus for OCD and ASDs at 9p24. We speculate that the area may represent a special candidate region for obsessive repetitive symptoms in ASDs.
In this study, three single-nucleotide polymorphisms (SNPs) on the lysyl oxidase-like 1 (LOXL1) g... more In this study, three single-nucleotide polymorphisms (SNPs) on the lysyl oxidase-like 1 (LOXL1) gene associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) were investigated in the Finnish population. A case-control study of 59 sporadic patients with XFS, 82 with XFG, 71 with primary open-angle glaucoma (POAG) and 26 individuals without these disorders from the southern Finnish population, and a family study of an extended family with 28 patients with XFS or XFG and 92 unaffected relatives from Kökar islands, Southwestern Finnish archipelago, were conducted. Anonymous blood donors (n=404) were studied as population-based controls. Three SNPs, rs1048661 (R141L), rs3825942 (G153D) and rs2165241, of the LOXL1 gene were genotyped by PCR sequencing. Association and linkage analyses were carried out. In both case-control and family materials, significant association for allele G of rs1048661 (P=2.65 x 10(-5); P=0.0007), allele G of rs3825942 (P=2.24 x 10(-8); P=0.49) and allele T of rs2165241 (P=2.62 x 10(-13); P<0.0001) was found in XFS/XFG. However, linkage was not observed for LOXL1 risk alleles. The corresponding three-locus haplotype GGT increased the risk of XFS/ XFG nearly 15-fold relative to low-risk haplotype GAC (odds ratio (OR): 14.9, P=1.6 x 10(-16)). In conclusion, the earlier reported polymorphisms of the LOXL1 gene showed significant association also in the Finnish population.
Music is listened in all cultures. We hypothesize that willingness to produce and perceive sound ... more Music is listened in all cultures. We hypothesize that willingness to produce and perceive sound and music is social communication that needs musical aptitude. Here, listening to music was surveyed using a web-based questionnaire and musical aptitude using the auditory structuring ability test (Karma Music test) and Carl Seashores tests for pitch and for time. Three highly polymorphic microsatellite markers (RS3, RS1 and AVR) of the arginine vasopressin receptor 1A (AVPR1A) gene, previously associated with social communication and attachment, were genotyped and analyzed in 31 Finnish families (n=437 members) using family-based association analysis. A positive association between the AVPR1A haplotype (RS1 and AVR) and active current listening to music (permuted P=0.0019) was observed. Other AVPR1A haplotype (RS3 and AVR) showed association with lifelong active listening to music (permuted P=0.0022). In addition to AVPR1A, two polymorphisms (5-HTTLPR and variable number of tandem repeat) of human serotonin transporter gene (SLC6A4), a candidate gene for many neuropsychiatric disorders and previously associated with emotional processing, were analyzed. No association between listening to music and the polymorphisms of SLC6A4 were detected. The results suggest that willingness to listen to music is related to neurobiological pathways affecting social affiliation and communication.
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