FTO genotype is associated with phenotypic variability of body mass index

There is evidence across several species for genetic control of phenotypic variation of complex traits1, 2, 3, 4, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ~170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)5, 6, 7, is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ~0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation9, 10. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

Martin Buber with Naemah Beer-Hofmann Portraits Groups

Handwritten on verso: Prof. Martin Buber mit Naemah Beer-Hofmann in meinem Zimmer, Kurhaus Sonn-Matt bei Luzern. September 1963 fuer meine leibe Lily an einem schweren Tag, der durch sie viel leichter wurde.

Painting of Freiherr Martin von Magnus Family Portraits Family

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Martin Riesenburger portrait portraits men

Martin Riesenburger (May 14, 1896 – Apr. 14, 1966) was Prediger (Preacher) for the Jewish community in Berlin-Weissensee throughout the Nazi era (protected by his gentile wife, Natalie Riesenburger). In 1953 he became Rabbi of the Jewish community in Berlin (East) and then Landesrabbiner of the German Democratic Republic.

Wedding portrait of Martin and Lotte Lewin Portraits Couples

Handwritten thank you note under photograph signed by Lotte Lewin dated February 6, 1935

Yasha and Riva outside their lighting store; Martin Luter Strasse, Berlin Portraits Couples

Relatives of the Judey-Barosin and Finkel families

Silver locket-style photograph frame containing portraits of Martin Wasserzug and Gaby Netter (later Glueckselig) Portraits Couples

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Martin Goldschmidt taking a morning walk and eating breakfast with the "Lavanguardia" newspaper; Barcelona Portraits Men

Born 1879?; Married September 2, 1903 in Leipzig to Paula Harmelin; Father of Henry H. Goldschmidt Gould and Ruth Augusta Beatrice Goldschmidt

Martin Goldschmidt and Paula Goldschmidt née Harmelin; Leipzig Portraits Couples

Paula Goldschmidt, née Harmelin, born 1880; Martin Goldschmidt, born circa 1879; Married September 2, 1903 in Leipzig

Studio portraits of Martin Goldschmidt Portraits Men

Born 1879?; Married September 2, 1903 in Leipzig to Paula Harmelin; Father of Henry H. Goldschmidt Gould and Ruth Augusta Beatrice Goldschmidt

Martin Goldschmidt in Prussian military uniform Portraits Men

Born 1879?; Married September 2, 1903 in Leipzig to Paula Harmelin, father of Henry H. Goldschmidt Gould and Ruth Augusta Beatrice Goldschmidt

Emilie Mosse and Anna Ginsberg walking in a park; Cape Martin Portraits; Groups; Women

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Der Prediger vom weißen Berg : Zur Rezeption der besseren Gerechtigkeit aus Mt 5 in Martin Luthers Predigtüberlieferung 1522 1546.

The purpose of this study is to examine the reception of Matthew 5 in Martin Luther s sermons; in other words to investigate how Luther interprets and applies Jesus teaching of the better righteousness and the law in Mt 5. The study applies the reception-historical approach and contributes to the history of effects and the history of interpretation in New Testament exegesis. The study shows that Luther understands the better righteousness of Mt 5 as good works and fulfillment of the law. Luther s interpretation coheres with the intention of the Evangelist, even if Luther s overall concept of righteousness is foreign to Matthew. In Luther s view righteousness is twofold: The greater righteousness of Mt 5 is the second and the actual righteousness (iustitia activa), which follows the first and the foreign righteousness (iustitia passiva). The first righteousness (faith) is for Luther the work of God, while the second righteousness (good works) is co-operation between a Christian and God. In this co-operation the law, as it is taught by Jesus, is not the opposite of the gospel, but the gospel itself in the sense of Christ as an example . The task of the law is to show the dependence of a Christian on God and to help one to love and to serve one s neighbour (brothers as well as enemies) properly. The study underlines a feature in Luther s thinking that has received little attention in Lutheran theology: Luther insists on preaching the law to Christians. In his view Mt 5 is directed to all Christians and particularly to pastors, for whom Jesus here gives an example of how to preach the law. Luther believes similarly to Matthew that Jesus reveals the real meaning of Mosaic Law and confirms its validity for Christians in Mt 5. Like Matthew, Luther insists on the practicability of the commandments of Mt 5 in his view Christians fulfil the law also with joy yet his interpretation of Mt 5 attenuates the radical nature of its commandments. Luther s reception of the individual pericopes of Mt 5 is considerably generative and occasionally contradictory, which is explained by the following factors, among others: Luther receives many ideas from tradition and reads them and his own theological concepts into Matthew s Gospel. He interprets Mt 5 through his understanding of some Old Testament passages as well as Paul. Most of all, Luther s reception of Mt 5 is shaped by his own experience as a preacher, by his relation to his religious enemies, rulers and to the congregation of Wittenberg. Here Luther shares with Matthew the experience of being opposed and concern about the upright living of the believers, which in both cases also explains the polemical tone of the paraenesis.

Claude Corty Collection 1994-2001

Family tree, genealogical notes and master chart for the Adler family in Warburg, prepared by Claude Corty.

Directional dominance on stature and cognition in diverse human populations

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3, 4. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5, 6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.