Combined genome scans for body stature in 6,602 European twins: evidence for common Caucasian loci.

Twin cohorts provide a unique advantage for investigations of the role of genetics and environment in the etiology of variation in common complex traits by reducing the variance due to environment, age, and cohort differences. The GenomEUtwin (http://www.genomeutwin.org) consortium consists of eight twin cohorts (Australian, Danish, Dutch, Finnish, Italian, Norwegian, Swedish, and United Kingdom) with the total resource of hundreds of thousands of twin pairs. We performed quantitative trait locus (QTL) analysis of one of the most heritable human complex traits, adult stature (body height) using genome-wide scans performed for 3,817 families (8,450 individuals) derived from twin cohorts from Australia, Denmark, Finland, Netherlands, Sweden, and United Kingdom with an approximate ten-centimorgan microsatellite marker map. The marker maps for different studies differed and they were combined and related to the sequence positions using software developed by us, which is publicly available (https://apps.bioinfo.helsinki.fi/software/cartographer.aspx). Variance component linkage analysis was performed with age, sex, and country of origin as covariates. The covariate adjusted heritability was 81% for stature in the pooled dataset. We found evidence for a major QTL for human stature on 8q21.3 (multipoint logarithm of the odds 3.28), and suggestive evidence for loci on Chromosomes X, 7, and 20. Some evidence of sex heterogeneity was found, however, no obvious female-specific QTLs emerged. Several cohorts contributed to the identified loci, suggesting an evolutionarily old genetic variant having effects on stature in European-based populations. To facilitate the genetic studies of stature we have also set up a website that lists all stature genome scans published and their most significant loci (http://www.genomeutwin.org/stature_gene_map.htm).

Genetic component of identification, intensity and pleasantness of odours: a Finnish family study.

Although potential odorant receptor genes have been identified, the precise genetic component of perception of odours is still obscure. Although there is some evidence for heritability of a few olfactory-related traits, no genome-wide search for loci harboring underlying genes has been published to date. We performed a genome-wide scan to identify loci affecting the identification, intensity and pleasantness of 12 odours (cinnamon, turpentine, lemon, smoke, chocolate, rose, paint thinner, banana, pineapple, gasoline, soap, onion) using 146 Finnish adults from 26 families. Several of these traits showed heritable variation in the families. Suggestive evidence of linkage was found for the pleasantness of cinnamon odour (h(2)=61%) on chromosome 4q32.3 (multipoint logarithm of the odds (LOD) score 3.01), as well as for the perceived intensity of paint thinner odour (h(2)=31%) on chromosome 2p14 (multipoint LOD score 2.55). As these loci do not contain any known human odorant receptor genes, they may rather harbor genes that affect the central processing than the peripheral detection of the odour signal. Thus, perception of odours is potentially modified by genes other than those encoding odorant receptors.

Sweet taste preferences are partly genetically determined: identification of a trait locus on chromosome 16.

BACKGROUND: Humans have an innate preference for sweet taste, but the degree of liking for sweet foods varies individually. OBJECTIVE: The proportion of inherited sweet taste preference was studied. A genome-wide linkage analysis was performed to locate the underlying genetic elements in the genome. DESIGN: A total of 146 subjects (32% men, 68% women) aged 18-78 y from 26 Finnish families evaluated the intensity and pleasantness of 3 suprathreshold solutions of sucrose (3.0%, 7.5%, and 18.75%) and plain water and the intensity of filter paper impregnated with 6-n-propylthiouracil (PROP). The subjects also reported the pleasantness and the use frequency of 5 sweet foods (chocolate, candy, ice cream, sweet desserts, and sweet pastry) and completed a food-behavior questionnaire that measured their craving for sweet foods. RESULTS: Of the chemosensory functions, the pleasantness rating of the strongest (18.75%) sucrose solution and the intensity rating of PROP yielded the highest heritability estimates (41% and 66%, respectively). The pleasantness and the use frequency of sweet foods (both variables calculated as a mean of ratings for 5 food items) and the craving for sweet foods showed significant heritability (40%, 50%, and 31%, respectively). A logarithm of odds score of 3.5 (P=0.00003) was detected for use frequency of sweet foods on chromosome 16p11.2 (marker D16S753). CONCLUSIONS: Sweet taste preferences are partly inherited. Chromosome 16p11.2 may harbor genetic variations that affect the consumption of sweet foods.

AUTOGSCAN: powerful tools for automated genome-wide linkage and linkage disequilibrium analysis.

Genome-wide linkage analysis using multiple traits and statistical software packages is a tedious process which requires a significant amount of manual file manipulation. Different linkage analysis programs require different input file formats, making the task of analyzing data with multiple methods even more time-consuming. We have developed a software tool, AUTOGSCAN, that automates file formatting, the running of statistical analyses, and the summarizing of resulting statistics for whole genome scans with a push of a button, using several independent, and often idiosyncratic, statistical software packages such as MERLIN, SOLAR and GENEHUNTER. We also describe a program, ANALYZE, designed to run qualitative linkage analysis with several different statistical strategies and programs to efficiently screen for linkage and linkage disequilibrium for a given discrete trait. The ANALYZE program can also be used by AUTOGSCAN in a genome-wide sense.

Genome-wide linkage screen for stature and body mass index in 3.032 families: evidence for sex- and population-specific genetic effects.

Stature (adult body height) and body mass index (BMI) have a strong genetic component explaining observed variation in human populations; however, identifying those genetic components has been extremely challenging. It seems obvious that sample size is a critical determinant for successful identification of quantitative trait loci (QTL) that underlie the genetic architecture of these polygenic traits. The inherent shared environment and known genetic relationships in family studies provide clear advantages for gene mapping over studies utilizing unrelated individuals. To these ends, we combined the genotype and phenotype data from four previously performed family-based genome-wide screens resulting in a sample of 9.371 individuals from 3.032 African-American and European-American families and performed variance-components linkage analyses for stature and BMI. To our knowledge, this study represents the single largest family-based genome-wide linkage scan published for stature and BMI to date. This large study sample allowed us to pursue population- and sex-specific analyses as well. For stature, we found evidence for linkage in previously reported loci on 11q23, 12q12, 15q25 and 18q23, as well as 15q26 and 19q13, which have not been linked to stature previously. For BMI, we found evidence for two loci: one on 7q35 and another on 11q22, both of which have been previously linked to BMI in multiple populations. Our results show both the benefit of (1) combining data to maximize the sample size and (2) minimizing heterogeneity by analyzing subgroups where within-group variation can be reduced and suggest that the latter may be a more successful approach in genetic mapping.

Heritability of adult body height: a comparative study of twin cohorts in eight countries.

A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.