Quantitative-Trait-Locus Analysis of Body-Mass Index and of Stature, by Combined Analysis of Genome Scans of Five Finnish Study Groups

Abstract

In recent years, many genomewide screens have been performed, to identify novel loci predisposing to various complex diseases. Often, only a portion of the collected clinical data from the study subjects is used in the actual analysis of the trait, and much of the phenotypic data is ignored. With proper consent, these data could subsequently be used in studies of common quantitative traits influencing human biology, and such a reanalysis method would be further justified by the nonbiased ascertainment of study individuals. To make our point, we report here a quantitative-trait-locus (QTL) analysis of body-mass index (BMI) and stature (i.e., height), with genotypic data from genome scans of five Finnish study groups. The combined study group was composed of 614 individuals from 247 families. Five study groups were originally ascertained in genetic studies on hypertension, obesity, osteoarthritis, migraine, and familial combined hyperlipidemia. Most of the families are from the Finnish Twin Cohort, which represents a population-wide sample. In each of the five genome scans, approximately 350 evenly spaced markers were genotyped on 22 autosomes. In analyzing the genotype data by a variance-component method, we found, on chromosome 7pter (maximum multipoint LOD score of 2.91), evidence for QTLs affecting stature, and a second locus, with suggestive evidence for linkage to stature, was detected on chromosome 9q (maximum multipoint LOD score of 2.61). Encouragingly, the locus on chromosome 7 is supported by the data reported by Hirschhorn et al. (in this issue), who used a similar method. We found no evidence for QTLs affecting BMI.

Combined analysis of genomewide scans for adult height: results from the NHLBI Family Blood Pressure Program

“…The heritability of height for the eight groups varied from 0.75 to 0.98, which is compatible with previous reports. [4][5][6] For individual genome scans, the region showing the strongest evidence for linkage was found in GENOA European Americans, centered at 14q21.1(MLS ¼ 3.67 at marker D14S592 ) ( Table 2). The same region also showed evidence of linkage in SAPPHIRe Asians with a LOD ¼ 1.60.…”

“…[1][2][3][4][5] Genetic studies of adult height have revealed that it is normally distributed, suggesting that height could be affected by the interaction of multiple genetic and environmental factors. Compared with other complex traits, adult height can be measured easily and accurately, reducing error variance in the phenotype.…”

“…Several recent genome scans for adult height revealed significant and suggestive evidence for linkage on several chromosomes. [4][5][6][7] However, few of these regions were replicated among different studies. This may not be surprising considering that height is a complex genetic trait affected by multiple genes, each having a small effect, as well as by environmental factors.…”

Fishing for Pleiotropic QTLs in a Polygenic Sea

“…Quantitative traits such as height, body mass index, blood pressure, visual acuity, and psychometric measures, that are routinely gathered in many epidemiological and genetic studies beg for proper analysis (Perola et al 2001). Longitudinal data such as that collected in the Framingham Heart Study also await more sophisticated treatment (Kraft et al 2003).…”

Meta‐Analysis of Linkage Studies for Complex Diseases: An Overview of Methods and a Simulation Study

“…GSMA needs at least one value of each study in each bin which is rarely the case if only interesting values are reported. However, more and more researchers distribute the detailed results of their analysis via the internet, such as NPL scores for each marker tested (as in a psoriasis scan by Nair et al 1997), where the multipoint statistics at regular intervals (as in a stature and BMI genome scan by Perola et al 2001) and the information content could be included. Besides, it is a long standing scientific tradition to retain data and intermediate results and to give other researchers the opportunity to verify the reported results by making materials and data available.…”