Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways

Girotto, Giorgia; Pirastu, Nicola; Sorice, Rossella; Biino, Ginevra; Campbell, Harry; D’Adamo, Pio; Hastie, Nicholas D.; Nutile, Teresa; Polašek, Ozren; Portas, Laura; Rudan, Igor; Ulivi, Sheila; Zemunik, Tatijana; Wright, Alan F.; Ciullo, Marina; Hayward, Caroline; Pirastu, Mario; Gasparini, Paolo

doi:10.1136/jmg.2010.088310

Cited by 72 publications

(92 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…None of the top-ranked SNPs in our study were statistically significant in any of the previous GWASs on ARHI. 4,5 To look for evidence of replication of previous studies, we first looked up the P-values for all individual SNPs that were reported to be significant in the previous GWASs and checked their significance in the current study. For the GWAS by Girotto et al, 5 this included the SNPs having a P-value below 10e À5.…”

Section: Common Variant Analysismentioning

confidence: 99%

Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment

et al. 2014

View full text Add to dashboard Cite

We performed a genome-wide association study (GWAS) to identify the genes responsible for age-related hearing impairment (ARHI), the most common form of hearing impairment in the elderly. Analysis of common variants, with and without adjustment for stratification and environmental covariates, rare variants and interactions, as well as gene-set enrichment analysis, showed no variants with genome-wide significance. No evidence for replication of any previously reported genes was found. A study of the genetic architecture indicates for the first time that ARHI is highly polygenic in nature, with probably no major genes involved. The phenotype depends on the aggregated effect of a large number of SNPs, of which the individual effects are undetectable in a modestly powered GWAS. We estimated that 22% of the variance in our data set can be explained by the collective effect of all genotyped SNPs. A score analysis showed a modest enrichment in causative SNPs among the SNPs with a P-value below 0.01.

show abstract

Section: Common Variant Analysismentioning

confidence: 99%

Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment

et al. 2014

View full text Add to dashboard Cite

show abstract

“…[28][29][30] In brief, INGI-CARL, INGI-FVG and INGI-VB have been genotyped with Illumina 370 k highdensity SNP array, whereas SR has been genotyped with Illumina 700 k highdensity SNP arrays. Genotype imputation on the INGI cohorts and SR was conducted after standard QC using SHAPEIT2 31 for the phasing step and IMPUTE2 32 for the imputation using the 1000 Genomes phase I v3 reference set.…”

Section: Genotyping and Imputationmentioning

confidence: 99%

Genome-wide association analysis on five isolated populations identifies variants of the HLA-DOA gene associated with white wine liking

Pirastu

Kooyman

Traglia³

et al. 2015

Eur J Hum Genet

View full text Add to dashboard Cite

Wine is the most popular alcoholic beverage around the world and because of its importance in society has been widely studied. Understanding what drives its flavor has been a quest for decades but much is still unknown and will be determined at least in part by individual taste preferences. Recently studies in the genetics of taste have uncovered the role of different genes in the determination of food preferences giving new insight on its physiology. In this context we have performed a genome-wide association study on red and white wine liking using three isolated populations collected in Italy, and replicated our results on two additional populations coming from the Netherland and Central Asia for a total of 3885 samples. We have found a significant association (P = 2.1 × 10 − 8 ) between white wine liking and rs9276975:C4T a polymorphism in the HLA-DOA gene encoding a non-canonical MHC II molecule, which regulates other MHC II molecules. The same association was also found with red wine liking (P = 8.3 × 10 − 6 ). Sex-separated analysis have also revealed that the effect of HLA-DOA is twice as large in women as compared to men suggesting an interaction between this polymorphism and gender. Our results are one of the first examples of genome-wide association between liking of a commonly consumed food and gene variants. Moreover, our results suggest a role of the MHC system in the determination of food preferences opening new insight in this field in general. INTRODUCTIONWine is probably the oldest produced beverage in human history dating its first apparition in Georgia 7000 BC. It is extremely important for many cultures not only for its economy but also from the social and religious point of view. For these reasons it is also the most common and consumed type of alcoholic beverage throughout the world. 1,2 In addition, several studies indicate that modest wine consumption can have some beneficial health effects, including protection against cardiovascular and Alzheimer's disease. [3][4][5][6] There has been extensive research aiming to improve both its production and its flavor. The taste of wine depends on many different sensory perceptions ranging from taste and olfaction to texture. 7 Wine is a mixture of thousands of molecules that can contribute to its final taste, 8 and its composition varies greatly depending on the grapes used, climate and production method. 9 Although the flavor of some of these compounds is very well known, it is really difficult to understand what their role in final taste is. 7,10,11 The relevant role of genetic factors both on alcohol consumption and dependence has been clearly demonstrated by genome-wide association study (GWAS) studies. [12][13][14][15][16] Moreover, studies on the genetic variations in bitter taste receptors have also shown that variations in TAS2R16 and TAS2R38 genes can influence alcohol intake [17][18][19] but not dependence. 19 On the contrary, very little is known about the possible contribution of genetic factors to alcohol preferences in humans. Recen...

show abstract

“…Moreover, a few single-gene, late-onset, dominant mutations have also been described, but these are rare, confirming the difficulties in dissecting the molecular basis of ARHL. Furthermore, quite recently, some genes associated with hearing functions, which might also play a role in ARHL, have been identified [32] . Finally, relatively few animal models of hearing impairment …”

Section: Age-related Hearing Lossmentioning

confidence: 99%

Consanguinity and Hereditary Hearing Loss in Qatar

et al. 2014

View full text Add to dashboard Cite

Qatar is a sovereign state located on the Eastern coast of the Arabian Peninsula in the Persian Gulf. Its native population consists of 3 major subgroups: people of Arabian origin or Bedouins, those from an Eastern or Persian ancestry and individuals with African admixture. Historically, all types of consanguineous marriages have been and still are common in the Qatari population, particularly among first and double-first cousins. Thus, there is a higher risk for most inherited diseases including hereditary hearing loss (HHL). In particular, a hearing loss prevalence of 5.2% has been reported in Qatar, with parental consanguinity being more common among affected individuals as compared with unaffected ones. Our recent molecular results confirm a high homogeneity and level of inbreeding in Qatari HHL patients. Among all HHL genes, GJB2, the major player worldwide, accounts for a minor proportion of cases and at least 3 additional genes have been found to be mutated in Qatari patients. Interestingly, one gene, BDP1, has been described to cause HHL only in this country. These results point towards an unexpected level of genetic heterogeneity despite the high level of inbreeding. This review provides an up-to-date picture of HHL in Qatar and of the impact of consanguinity on this disease.

show abstract

Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways

Cited by 72 publications

References 38 publications

Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment

Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment

Genome-wide association analysis on five isolated populations identifies variants of the HLA-DOA gene associated with white wine liking

Consanguinity and Hereditary Hearing Loss in Qatar

Contact Info

Product

Resources

About